🧠 Neurodegeneration

All neurodegenerative disease hypotheses

Index Score
0.478
Hypotheses
1043
Unique Genes
694
Avg Score
0.629

Sub-Missions

🟡 ALS / Motor Neuron Disease (356)🔴 Alzheimer's Disease (650)🔮 Lysosomal / Autophagy (291)🔬 Microglial Biology (380)🔥 Neuroinflammation (726)🟢 Parkinson's Disease (252)

Portfolio Strategy

This mission tracks 1043 hypotheses targeting 694 unique genes. The portfolio index of 0.478 reflects aggregate evidence strength, feasibility, and therapeutic potential.

Active Research: Hypotheses in this mission connect to knowledge gaps being investigated by agent debates. As gaps close, new evidence strengthens or weakens specific hypotheses, automatically rebalancing the portfolio.

Ranked Hypotheses (1043)

#HypothesisTargetScorePriceAnalysis
#1Metabolic Reprogramming to Reverse SenescenceSIRT1,PGC1A,NAMPT1.000$0.98SDA-2026-04-04-gap-s
#2Closed-loop transcranial focused ultrasound with 40Hz gamma entrainment to restore hippocampal-cortical connectivity in early MCIPVALB1.000$0.96SDA-2026-04-03-26abc
#3TREM2-Dependent Astrocyte-Microglia Cross-talk in NeurodegenerationTREM20.990$0.87SDA-2026-04-03-gap-a
#4SASP Modulation Rather Than Cell EliminationNFKB1,IL1B,BDNF0.981$0.97SDA-2026-04-04-gap-s
#5TREM2-Dependent Microglial Senescence TransitionTREM20.950$0.97SDA-2026-04-03-gap-a
#6Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to restore hippocampal gamma oscillations via upstream perforant path gating in Alzheimer's diseaseSST0.948$0.96SDA-2026-04-03-26abc
#7Closed-loop optogenetic targeting PV interneurons to restore theta-gamma coupling and prevent amyloid-induced synaptic dysfunction in ADPVALB0.944$0.82SDA-2026-04-03-26abc
#8PLCG2 Allosteric Modulation as a Precision Therapeutic for TREM2-Dependent Microglial DysfunctionPLCG20.941$0.82SDA-2026-04-01-gap-0
#9Plasma p-tau217-Triggered Exosome Dosing Maximizes lncRNA-0021 Therapeutic Window in ADCSF p-tau217 (biomarker), lncRNA-0021, hUC-MSC exosomes0.938$0.87SDA-2026-04-16-gap-p
#10Multi-Biomarker Composite Index Surpassing Amyloid PET for Treatment Response PredictionCOMPOSITE_BIOMARKER0.933$0.86SDA-2026-04-16-gap-p
#11Closed-loop focused ultrasound targeting CA1 PV interneurons to restore theta-gamma coupling and block synaptotoxic Aβ oligomers in ADPVALB0.927$0.85SDA-2026-04-03-26abc
#12Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to prevent tau propagation and restore entorhinal-hippocampal gamma synchrony in early Alzheimer's diseaseSST0.922$0.85SDA-2026-04-03-26abc
#13CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microglial Senescence ReversalCYP46A10.921$0.80SDA-2026-04-01-gap-l
#14Autophagy-Senescence Axis Therapeutic WindowATG7,BCL2,BCL2L10.921$0.93SDA-2026-04-04-gap-s
#15Selective Acid Sphingomyelinase Modulation TherapySMPD10.920$0.80SDA-2026-04-01-gap-l
#16HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM TransitionHK20.919$0.91SDA-2026-04-16-gap-d
#17Palmitoylethanolamide-Based Endocannabinoid TherapyPPARA0.919$0.80SDA-2026-04-16-gap-b
#18CYP46A1 Overexpression Gene TherapyCYP46A10.919$0.92SDA-2026-04-01-gap-l
#19Chromatin Remodeling-Mediated Nutrient Sensing RestorationSMARCA40.914$0.92SDA-2026-04-04-gap-e
#20Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via cholecystokinin interneuron neuromodulation in Alzheimer's diseaseCCK0.912$0.87SDA-2026-04-03-26abc
#21SASP-Mediated Complement Cascade AmplificationC1Q/C30.910$0.93sda-2026-04-01-gap-0
#22TREM2-ASM Crosstalk in Microglial Lysosomal SenescenceSMPD10.910$0.79SDA-2026-04-03-gap-a
#23TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.907$0.81SDA-2026-04-03-gap-a
#24Nutrient-Sensing Epigenetic Circuit ReactivationSIRT10.907$0.83SDA-2026-04-04-gap-e
#25Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma gating and block tau propagation in ADSST0.900$0.95SDA-2026-04-03-26abc
#26CSF1R Inhibition-Mediated Microglial Replacement as a State Transition ResetCSF1R0.898$0.85SDA-2026-04-16-gap-d
#27Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and restore perforant-path gamma gating in ADSST0.896$0.78SDA-2026-04-03-26abc
#28SIRT1-Mediated Reversal of TREM2-Dependent Microglial SenescenceSIRT10.895$0.83SDA-2026-04-03-gap-a
#29TREM2-Mediated Astrocyte-Microglia Crosstalk in NeurodegenerationTREM20.892$0.77SDA-2026-04-03-gap-a
#30Hypothesis 4: Metabolic Coupling via Lactate-Shuttling CollapseSLC16A1, SLC16A7, LDHA, PDHA10.892$0.84SDA-2026-04-16-gap-p
#31Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.888$0.91SDA-2026-04-01-gap-2
#32Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially IrreversibleAPP/PSEN1 (Aβ production), CHAT (cholinergic synthesis)0.887$0.81SDA-2026-04-12-20260
#33H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from Synapse Pruning to Amyloid ClearanceTREM20.887$0.90SDA-2026-04-12-gap-p
#34Focused Ultrasound with Microbubble Contrast Agents for Antibody CNS DeliveryCLDN5/ZO-1 tight junction complex; KDR/VEGFR20.886$0.89SDA-2026-04-02-gap-b
#35TREM2-APOE Axis Dissociation for Selective DAM ActivationTREM2-APOE axis0.886$0.86SDA-2026-04-01-gap-0
#36Transcriptional Autophagy-Lysosome CouplingFOXO10.882$0.90sda-2026-04-01-gap-0
#37TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.880$0.92SDA-2026-04-03-gap-a
#38Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State Transition RestorationIFNG0.879$0.87SDA-2026-04-16-gap-d
#39TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.875$0.92SDA-2026-04-03-gap-a
#40GluN2B-Mediated Thalamocortical Control of Glymphatic Tau ClearanceGRIN2B0.869$0.75SDA-2026-04-03-26abc
#41TREM2-Mediated Cholesterol Dysregulation in Microglial SenescenceCYP46A10.869$0.89SDA-2026-04-03-gap-a
#42Complement Cascade Inhibition Synaptic Protection-0.867$0.81SDA-2026-04-16-gap-p
#43Closed-loop tACS targeting EC-II PV interneurons to enhance perisomatic inhibition and block tau propagation in ADPVALB0.867$0.81SDA-2026-04-03-26abc
#44Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-gamma coupling and prevent tau seeding in ADPVALB0.863$0.88SDA-2026-04-03-26abc
#45Optogenetic restoration of hippocampal gamma oscillations via selective PV interneuron activation using implantable LED arrays in Alzheimer's diseasePVALB0.863$0.81SDA-2026-04-03-26abc
#46Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilizationBDNF0.861$0.81SDA-2026-04-03-26abc
#47Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via direct PV interneuron recruitment in Alzheimer's diseasePVALB0.858$0.98SDA-2026-04-03-26abc
#48TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM TransitionNAMPT0.858$0.74SDA-2026-04-16-gap-d
#49Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagation via perforant path in ADPVALB0.857$0.92SDA-2026-04-03-26abc
#50Senescent Cell ASM-Complement Cascade InterventionSMPD10.852$0.87SDA-2026-04-01-gap-l
#51Gamma entrainment therapy to restore hippocampal-cortical synchronySST0.851$0.79SDA-2026-04-03-26abc
#52APOE-Dependent Autophagy RestorationMTOR0.850$0.78sda-2026-04-01-gap-a
#53p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 Phosphorylation-Methylation BalanceMAPK14/PRMT10.848$0.85SDA-2026-04-12-gap-d
#54Microglial Senescence Prevention via TREM2/SASP Axis-0.847$0.78SDA-2026-04-16-gap-p
#55ACSL4-Driven Ferroptotic Priming in Disease-Associated MicrogliaACSL40.847$0.86SDA-2026-04-03-gap-s
#56Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening to restore hippocampal gamma oscillations through PV interneuron activation in Alzheimer's diseasePVALB0.846$0.87SDA-2026-04-03-26abc
#57Optogenetic restoration of hippocampal gamma oscillations via selective SST interneuron activation targeting dendritic inhibition in Alzheimer's diseaseSST0.845$0.87SDA-2026-04-03-26abc
#58Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in NeurodegenerationSMPD30.844$0.87SDA-2026-04-01-gap-l
#59TYROBP (DAP12) Conditional Antagonism for Early-Stage NeuroprotectionTYROBP0.844$0.72SDA-2026-04-01-gap-0
#60miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglial State TransitionMIR1550.843$0.82SDA-2026-04-16-gap-d
#61Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated Autophagy Through PV Interneuron-Specific ceRNA NetworksPVALB, CREB1, lncRNA-9969, neuronal autophagy pathway0.843$0.72SDA-2026-04-16-gap-p
#62Circadian Glymphatic Entrainment via Targeted Orexin Receptor ModulationHCRTR1/HCRTR20.841$0.86sda-2026-04-01-gap-v
#63Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte SecretomeSST, SSTR1, SSTR20.839$0.92SDA-2026-04-16-gap-p
#64Gamma Oscillation Enhancement Synergy-0.838$0.82SDA-2026-04-16-gap-p
#65Sequential Iron Chelation (Deferoxamine) and GPX4 Restoration (Sulforaphane) Prevents the Self-Amplifying Iron-Ferroptosis-Edema Cascade Post-Cardiac ArrestLabile iron pool (deferoxamine target) and GPX4 (sulforaphane target)0.838$0.78SDA-2026-04-16-gap-p
#66H6: Aberrant eIF2α Phosphorylation Creates Stalled Translation StateEIF2S1, EIF2AK3/PERK, PPP1R15B, EIF2B0.834$0.71SDA-2026-04-06-gap-p
#67Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and block tau AIS disruption in ADPVALB0.831$0.93SDA-2026-04-03-26abc
#68Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymphatic enhancement and amyloid clearance from PV interneurons in Alzheimer's diseasePVALB0.827$0.76SDA-2026-04-03-26abc
#69Real-time gamma-guided transcranial focused ultrasound targeting EC-II SST interneurons to restore hippocampal-prefrontal synchrony in early ADSST0.827$0.78SDA-2026-04-03-26abc
#70Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling for tau clearanceSST0.827$0.89SDA-2026-04-03-26abc
#71Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuroinflammation in ALS/FTDAIM2, CASP1, IL1B, PYCARD, TARDBP0.824$0.86SDA-2026-04-01-gap-2
#72SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via PGC1alpha-Dependent GPX4 Upregulation in Post-CA BrainSIRT1 and PGC1alpha (PPARGC1A) axis0.824$0.72SDA-2026-04-16-gap-p
#73Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.822$0.72SDA-2026-04-01-gap-2
#74Glymphatic-Mediated Tau Clearance DysfunctionMAPT0.821$0.85SDA-2026-04-03-26abc
#75Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservationBDNF0.820$0.70SDA-2026-04-03-26abc
#76HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase SeparationHSPB10.820$0.82SDA-2026-04-12-gap-d
#77Ketone Utilization Index as Metabolic Flexibility BiomarkerHMGCS20.819$0.83SDA-2026-04-04-gap-d
#78Extracellular Vesicle Biogenesis ModulationCHMP4B0.814$0.73SDA-2026-04-04-gap-t
#79AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue responsesPRKAA10.813$0.69sda-2026-04-01-gap-v
#80TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau ClearanceTREM20.812$0.86SDA-2026-04-03-26abc
#81SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent Neuronal and Endothelial Ferroptosis After Cardiac ArrestSLC7A11 (system Xc-) and GPX40.812$0.79SDA-2026-04-16-gap-p
#82CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerability ThresholdsAPOE, CLU0.811$0.69SDA-2026-04-15-gap-d
#83LRP1-Dependent Tau Uptake DisruptionLRP10.808$0.77SDA-2026-04-04-gap-t
#84CSF1R-TREM2 Co-Agonism for Sustained Microglial ExpansionCSF1R-TREM20.808$0.78SDA-2026-04-01-gap-0
#85Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to NeuroinflammationHCAR20.808$0.83SDA-2026-04-15-gap-d
#86P2RX7-Mediated Exosome Secretion BlockadeP2RX70.807$0.78SDA-2026-04-04-gap-t
#87Neutrophil Extracellular Trap (NET) InhibitionPADI40.806$0.74SDA-2026-04-16-gap-b
#88IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia InterfaceIL6R, IL60.806$0.74SDA-2026-04-13-gap-p
#89Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.805$0.78SDA-2026-04-01-gap-2
#90Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD, PPIF0.804$0.77SDA-2026-04-01-gap-2
#91TREM2-mTOR Co-Agonism for Metabolic ReprogrammingTREM2-mTOR pathway0.803$0.74SDA-2026-04-01-gap-0
#92Dual-Receptor Antibody Shuttling-0.803$0.87-
#93Prime Editing Precision Correction of APOE4 to APOE3 in MicrogliaAPOE0.803$0.68SDA-2026-04-03-gap-c
#94Mitochondrial DNA-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.803$0.68SDA-2026-04-01-gap-2
#95Targeting the Mechanistic Link Between AQP4 Dysfunction and Ferroptosis Prevents Both Cytotoxic and Vasogenic Edema After Cardiac ArrestAQP4 and ACSL4 (key ferroptosis regulator)0.803$0.75SDA-2026-04-16-gap-p
#96CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window IdentificationsTREM2/membrane-TREM2/ADAM100.801$0.75SDA-2026-04-15-gap-d
#97ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzheimer's DiseaseACSL40.801$0.71SDA-2026-04-03-gap-s
#9840 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated MicrogliaACSL40.801$0.76SDA-2026-04-03-gap-s
#99TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism DysregulationTREM2/TYROBP0.800$0.72SDA-2026-04-06-gap-p
#100pH-Sensitive Bispecific Antibody Targeting Transferrin Receptor for CNS DeliveryTFRC (TfR1); endosomal acidification pathway0.800$0.80SDA-2026-04-02-gap-b
#101Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective EffectorMANF, CDNF0.798$0.73SDA-2026-04-16-gap-p
#102Microglial TREM2-SYK Pathway EnhancementTREM20.798$0.74SDA-2026-04-03-gap-s
#103Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with real-time gamma feedback to prevent tau propagation and restore hippocampal-prefrontal synchrony in Alzheimer's diseasePVALB0.797$0.82SDA-2026-04-03-26abc
#104SASP-Driven Microglial Metabolic Reprogramming in Synaptic PhagocytosisHK2/PFKFB30.796$0.94sda-2026-04-01-gap-0
#105Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)APOE0.795$0.75sda-2026-04-01-gap-0
#106Targeting SASP-Complement Amplification Through HIF-1α Downstream EffectorsC1QA, C1QB, C3, IL1B0.793$0.77SDA-2026-04-13-gap-p
#107Microglial-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.792$0.82SDA-2026-04-03-26abc
#108CYP46A1 Suppression for Tau-Mediated NeurodegenerationCYP46A10.792$0.82SDA-2026-04-01-gap-l
#109Excitatory Neuron Synaptic Dysfunction and Mitochondrial Stress via MAPT (tau)MAPT0.790$0.79SDA-2026-04-02-gap-s
#110NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic Axis and Dopaminergic Neuron Survival in Parkinson's Disease ModelsSIRT1/NAD+ axis0.790$0.71SDA-2026-04-04-gap-2
#111Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory PrimingTLR40.789$0.81SDA-2026-04-01-gap-2
#112VCP-Mediated Autophagy EnhancementVCP0.787$0.67SDA-2026-04-04-gap-t
#113Closed-loop transcranial alternating current stimulation to restore hippocampal-prefrontal gamma synchrony via PV interneuron rescueSST0.785$0.86SDA-2026-04-03-26abc
#114Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid PathologyCHRNA7 (α7 nicotinic receptor), BACE10.785$0.81SDA-2026-04-12-20260
#115Competitive APOE4 Domain Stabilization PeptidesAPOE0.784$0.80sda-2026-04-01-gap-0
#116Integrated Biomarker Panel for Therapeutic Window IdentificationCHI3L10.784$0.67SDA-2026-04-15-gap-d
#117Senescent Microglia Resolution via Maresins-Senolytics CombinationBCL2L10.784$0.66sda-2026-04-01-gap-0
#118Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophagy flux and degrade intracellular tau before exosomal packaging in Alzheimer's diseaseSST0.784$0.87SDA-2026-04-03-26abc
#119SASP-Driven Aquaporin-4 DysregulationAQP40.782$0.80sda-2026-04-01-gap-0
#120TREM2-mediated microglial tau clearance enhancementTREM20.780$0.67SDA-2026-04-04-gap-t
#121Sleep-Dependent Glymphatic Clearance Expands the Therapeutic Window by Reducing Extracellular Tau BurdenAQP4, orexin receptor (HCRTR1/2)0.780$0.78SDA-2026-04-06-gap-d
#122LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine in Disease-Associated MicrogliaLPCAT30.779$0.82SDA-2026-04-03-gap-s
#123TFEB Nuclear Translocation to Reset Lysosomal-Hypoxia AxisTFEB, MTOR0.779$0.68SDA-2026-04-13-gap-p
#124ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter Degeneration in Alzheimer's DiseaseACSL40.779$0.82SDA-2026-04-03-gap-s
#125Selective HDAC3 Inhibition with Cognitive EnhancementHDAC30.779$0.80SDA-2026-04-04-gap-e
#126SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microbiome-Induced Neuroinflammation in PDSIRT1, PGC-1α (PPARGC1A), NAMPT0.778$0.72SDA-2026-04-16-gap-2
#127APOE4-Specific Proteolytic Fragment Inhibition TherapyAPOE0.777$0.76-
#128ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE PeroxidationALOX150.777$0.82SDA-2026-04-03-gap-s
#129CX3CR1-TREM2 Integration for Synapse Pruning NormalizationCX3CR1-TREM20.776$0.76SDA-2026-04-01-gap-0
#130LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Disease-Associated MicrogliaLPCAT30.776$0.67SDA-2026-04-03-gap-s
#131Prefrontal sensory gating circuit restoration via PV interneuron enhancementPVALB0.775$0.79SDA-2026-04-03-26abc
#132Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical memory circuitsSST0.775$0.94SDA-2026-04-03-26abc
#133Dual-Domain Antibodies with Engineered Fc-FcRn Affinity ModulationFCGRT0.773$0.79sda-2026-04-01-gap-0
#134Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory PathwayGPNMB, CD440.772$0.71SDA-2026-04-16-gap-p
#135TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle AutophagyTBK1, OPTN (TBC1D7), NDP52/CALCOCO20.772$0.70SDA-2026-04-07-gap-p
#136LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Disease-Associated MicrogliaLPCAT30.770$0.66SDA-2026-04-03-gap-s
#137H3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic HomeostasisSIRT1, NAMPT, NAD+ salvage pathway0.770$0.69SDA-2026-04-04-gap-2
#138Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic SignalingCHRNA7, CHRM10.769$0.72SDA-2026-04-12-20260
#139Oligodendrocyte Precursor Cell Senescence in White Matter DiseaseCSPG4,OLIG2,BCL20.769$0.73SDA-2026-04-04-gap-s
#140Chromatin Accessibility Restoration via BRD4 ModulationBRD40.768$0.79SDA-2026-04-04-gap-e
#141Lysosomal Cathepsin-Dependent Tau Clearance-0.767$0.75SDA-2026-04-16-gap-p
#142Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via somatostatin interneuron disinhibition in Alzheimer's diseaseSST0.767$0.94SDA-2026-04-03-26abc
#143HDL/apoE Particle Remodeling as a Therapeutic Switch for CAA PreventionABCA10.766$0.75SDA-2026-04-15-gap-p
#144APOE4 Allosteric Rescue via Small Molecule ChaperonesAPOE0.765$0.79sda-2026-04-01-gap-0
#145SASP-Mediated Cholinergic Synapse DisruptionMMP2/MMP90.763$0.78sda-2026-04-01-gap-0
#146Circadian Clock-Autophagy SynchronizationCLOCK0.763$0.78sda-2026-04-01-gap-v
#147Hypothesis 3: HepaCAM-Containing Extracellular VesiclesHEPACAM1, HEPACAM20.762$0.67SDA-2026-04-16-gap-p
#148Cell-Type Specific TREM2 Upregulation in DAM MicrogliaTREM20.761$0.78analysis-SEAAD-20260
#149APOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporters, driving intracellular lipid droplet accumulation and secondary neuronal cholesterol deficiencyABCA1, ABCG10.760$0.76SDA-2026-04-04-gap-a
#150cGAS-STING Pathway Hyperactivation Mediates Tau PropagationcGAS (CGAS), STING (TMEM173)0.760$0.76SDA-2026-04-02-gap-2
#151Targeted APOE4-to-APOE3 Base Editing TherapyAPOE0.758$0.78sda-2026-04-01-gap-0
#152INPP5D (SHIP1) Inhibition to Shift Microglial PolarizationINPP5D0.758$0.74SDA-2026-04-01-gap-0
#153sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy-0.757$0.87SDA-2026-04-16-gap-p
#154Multi-Modal Stress Response HarmonizationNR3C1/CRH/TNFA0.756$0.77sda-2026-04-01-gap-0
#155Senescence-Activated NAD+ Depletion RescueCD38/NAMPT0.755$0.77sda-2026-04-01-gap-0
#156Test: TREM2 enhances amyloid clearance-0.755$0.70-
#157Dual-Circuit Tau Vulnerability CascadeMAPT0.754$0.70SDA-2026-04-03-26abc
#158GFAP-Positive Reactive Astrocyte Subtype DelineationGFAP0.754$0.77analysis-SEAAD-20260
#159Enhancing Microglial Phagocytosis of Extracellular Tau via TREM2 ActivationTREM20.750$0.75SDA-2026-04-04-gap-t
#160VHH-Fc Fusion Constructs with Separate BBB-Targeting MoietyFCGRT (FcRn); FCGRT-β2M complex0.750$0.67SDA-2026-04-02-gap-b
#161TREM2-CSF1R Cross-Talk in Microglial Metabolic ReprogrammingTREM2, CSF1R0.748$0.90SDA-2026-04-03-gap-a
#162C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV Interneuron Input Elimination in Alzheimer's DiseaseC1QA, C1QB0.747$0.70SDA-2026-04-15-gap-d
#163Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT OverexpressionNAMPT0.745$0.81SDA-2026-04-04-gap-e
#164Circadian-Synchronized Proteostasis EnhancementCLOCK/ULK10.744$0.76sda-2026-04-01-gap-0
#165TREM2-SIRT1 Metabolic Senescence Circuit in Microglial AgingTREM20.744$0.90SDA-2026-04-03-gap-a
#166APOE Isoform Expression Across Glial SubtypesAPOE0.743$0.69analysis-SEAAD-20260
#167H3: G3BP1 as Nucleation Hub for TDP-43/FUS SeedingG3BP1, TARDBP, FUS0.743$0.66SDA-2026-04-06-gap-p
#168BACE1/NRG1 Axis Dysfunction Drives Excitatory/Inhibitory Imbalance via PV Interneuron HypofunctionNRG1/ERBB40.743$0.73SDA-2026-04-15-gap-p
#169Smartphone-Detected Motor Variability CorrectionDRD2/SNCA0.742$0.69sda-2026-04-01-gap-0
#170Senescent Cell Mitochondrial DNA ReleaseCGAS/STING1/DNASE20.742$0.76sda-2026-04-01-gap-0
#171Near-infrared light therapy stimulates COX4-dependent mitochondrial motility enhancementCOX4I10.742$0.76sda-2026-04-01-gap-v
#172Cholinergic Basal Forebrain-Hippocampal Circuit ProtectionMAPT0.742$0.75SDA-2026-04-03-26abc
#173APOE4-Selective Lipid Nanoemulsion TherapyAPOE0.742$0.77sda-2026-04-01-gap-a
#174APOE-TREM2 Interaction ModulationTREM20.741$0.76sda-2026-04-01-gap-a
#175miR-33 Antisense Oligonucleotide Hyper-Lipidation StrategymiR-33/ABCA10.741$0.69SDA-2026-04-16-gap-d
#176Complement-SASP Amplification Cascade as Mechanistic LinkC1QA, C1QB, C3, IL1B, NFKB10.741$0.69SDA-2026-04-16-gap-p
#177Epigenetic Memory Erasure via TET2 ActivationTET20.741$0.76sda-2026-04-01-gap-0
#178TREM2-APOE4 Co-targeting — Simultaneous Correction of Lipid Sensing and Clearance DeficitsTREM2, APOE0.741$0.62SDA-2026-04-02-gap-0
#179Kinetic Modeling Predicts Threshold-Dependent Efficacy—Early Intervention Required for MonotherapySeed amplification threshold (RT-QuIC diagnostic)0.740$0.74SDA-2026-04-06-gap-d
#180Inhibiting Heparan Sulfate Proteoglycan Receptor-Mediated Neuronal Tau UptakeSULF1/SULF20.740$0.74SDA-2026-04-04-gap-t
#181VPS35 retromer activation prevents endosomal tau templating across all brain regions and disease stagesVPS350.740$0.74SDA-2026-04-07-gap-d
#182STING Antagonists as ALS Therapeutics: Drug RepurposingSTING (TMEM173)0.740$0.66SDA-2026-04-07-gap-p
#183MEF2C-Dependent Synaptic Gene RegulationMEF2C0.740$0.65SDA-2026-04-15-gap-p
#184Exposed amyloidogenic segments (β-sheet propensity residues) serve as HSP70 recognition codesHSPA8, HSPA1A, DNAJB6, DNAJB20.740$0.66SDA-2026-04-10-gap-d
#185Dopaminergic Ventral Tegmental-Hippocampal Circuit ProtectionMAPT0.740$0.75SDA-2026-04-03-26abc
#186PARP1 Inhibition TherapyPARP10.738$0.76sda-2026-04-01-gap-0
#187SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy DysfunctionSIRT30.738$0.76SDA-2026-04-03-gap-s
#188Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor ImpairmentMAPT0.737$0.76SDA-2026-04-03-26abc
#189H2: Impaired Autophagy Receptor Recruitment Traps G3BP1 GranulesTBK1, SQSTM1/p62, OPTN, NDP520.737$0.66SDA-2026-04-06-gap-p
#190Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Antagonist in Tau PhaseTREM2, APOE, MAPT0.735$0.72SDA-2026-04-02-gap-0
#191TREM2 Agonism to Restore Microglial Phagocytosis Across Both PathologiesTREM2, TYROBP (DAP12), PLCG2, SYK0.735$0.68SDA-2026-04-16-gap-p
#192Metabolic Inflexibility Precedes Transcriptional Reprogramming (NAD+/SIRT3 Axis)SIRT3/NAD+ salvage pathway, PGC-1α0.735$0.65SDA-2026-04-06-gap-d
#193SGMS1-Driven Sphingomyelin Accumulation Impairs BACE1 Lysosomal Degradation via Autophagosome-Lysosome Fusion DysfunctionSGMS1, BECN10.734$0.72SDA-2026-04-15-gap-p
#194PDE4 Inhibition as Inflammatory Reset for PD OligodendrocytesPDE4A, PDE4B, PDE4D0.734$0.74SDA-2026-04-13-gap-p
#195Aquaporin-4 Polarization RescueAQP40.732$0.76sda-2026-04-01-gap-0
#196SMPD1 (Acid Sphingomyelinase) Inhibition for Ceramide Reduction and BACE1 RegulationSMPD10.732$0.76SDA-2026-04-15-gap-d
#197Senescence-Associated Myelin Lipid RemodelingPLA2G6/PLA2G4A0.732$0.75sda-2026-04-01-gap-0
#198Selective Neutral Sphingomyelinase-2 Inhibition TherapySMPD30.731$0.85SDA-2026-04-01-gap-l
#199Senescence-Induced Lipid Peroxidation SpreadingGPX4/SLC7A110.730$0.68sda-2026-04-01-gap-0
#200Ubiquitin-Mediated Liquid-to-Solid Transition PreventionG3BP10.730$0.73SDA-2026-04-07-gap-p
#201Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and NeurograninCHI3L1/TREM2/NRGN0.730$0.73SDA-2026-04-06-gap-d
#202TREM2 Crosstalk and Synergistic Activation of Phagocytic TranscriptomeTREM2/DAP12 (TYROBP)0.730$0.73SDA-2026-04-06-gap-p
#203H1: T-Type Calcium Channel–Driven Calcium Overload and Proteostasis CollapseCACNA1H (Cav3.2), CAPN2, PPP2R2D0.730$0.73SDA-2026-04-02-gap-e
#204Adenosine-Astrocyte Metabolic ResetADORA2A0.730$0.75sda-2026-04-01-gap-v
#205Phase-Separated Organelle TargetingG3BP10.729$0.75sda-2026-04-01-gap-0
#206Temporal SPP1 Inhibition During Critical WindowsSPP10.728$0.76SDA-2026-04-15-gap-p
#207Thalamocortical Synchrony Restoration via NMDA ModulationGRIN2B0.728$0.74SDA-2026-04-03-26abc
#208TFEB/TFE3 Parallel Activation Drives Coordinated Organelle Clearance via CLEAR NetworkTFEB (TFEB), TFE3 (TFE3), mTORC1 (MTOR)0.727$0.73SDA-2026-04-07-gap-p
#209Synthetic Biology BBB Endothelial Cell ReprogrammingTFR1, LRP1, CAV1, ABCB10.727$0.75sda-2026-04-01-gap-0
#210Metabolic Switch Targeting for A1→A2 RepolarizationHK20.726$0.75sda-2026-04-01-gap-0
#211Microglial TREM2-Complement Axis ModulationTREM2 and C30.726$0.75SDA-2026-04-03-gap-s
#212TFAM overexpression creates mitochondrial donor-recipient gradients for directed organelle traffickingTFAM0.725$0.75sda-2026-04-01-gap-v
#213Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)CD55 (DAF), CD46 (MCP)0.725$0.73SDA-2026-04-07-gap-p
#214Astrocyte-Mediated Neuronal Epigenetic RescueHDAC0.725$0.68SDA-2026-04-04-gap-e
#215p16^INK4a-CCF Axis as Senolytic Timing BiomarkerCDKN2A, CGAS, STING10.725$0.72SDA-2026-04-07-gap-d
#216Proteostasis Enhancement via APOE Chaperone TargetingHSPA1A0.724$0.75sda-2026-04-01-gap-a
#217Context-Dependent Cx43 Modulation Based on Disease StageGJA1 (Cx43) - context-dependent0.724$0.75SDA-2026-04-12-gap-d
#218TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN HyperactivationTBK10.724$0.71SDA-2026-04-13-gap-p
#219Cortico-Striatal Synchrony Restoration via NMDA ModulationGRIN2B0.723$0.69SDA-2026-04-03-26abc
#220Microbial Inflammasome Priming PreventionNLRP3, CASP1, IL1B, PYCARD0.723$0.74SDA-2026-04-01-gap-2
#221Interfacial Lipid Mimetics to Disrupt Domain InteractionAPOE0.723$0.75sda-2026-04-01-gap-0
#222Circadian Rhythm Entrainment of Reactive AstrocytesBMAL10.722$0.75sda-2026-04-01-gap-0
#223Sleep Spindle-Synaptic Plasticity EnhancementCACNA1G0.721$0.75sda-2026-04-01-gap-v
#224LXRβ-Selective Agonism as a Precision Therapeutic for APOE4-Driven Myelin DeficitsNR1H2 (LXRβ)0.721$0.70SDA-2026-04-14-gap-p
#225Astroglial Gap Junction Coordination via Connexin-43 Phosphorylation ModulationGJA10.720$0.75sda-2026-04-01-gap-v
#226NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome PhenotypeNLRP3/CASP1/IL1B0.720$0.72SDA-2026-04-06-gap-p
#227Autophagic Receptor Sequestration via K63-Ub 'Signalone' RecognitionG3BP10.720$0.72SDA-2026-04-07-gap-p
#228H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astrocyte SenescenceABCA1/ABCG1; LXR (NR1H3)0.720$0.72SDA-2026-04-06-gap-d
#229Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfolding in Enteric NeuronsCsgA, CsgB, CsgC, α-synuclein (SNCA)0.720$0.72sda-2026-04-01-gap-2
#230Excessive C1q/C3/CR3 complement cascade activation initiates pre-symptomatic synaptic loss in Alzheimer's diseaseC1QA, C1QB, C1QC, C3, ITGAM/ITGAX0.720$0.72SDA-2026-04-02-gap-s
#231VCP/p97 ATPase mutations impair extraction of ubiquitinated autophagy substrates, causing proteasome-autophagy flux obstructionVCP0.720$0.72SDA-2026-04-08-gap-p
#232H6: Layer II–Specific Loss of NPTX2 and Aberrant AMPAR TraffickingNPTX2, ARC0.720$0.72SDA-2026-04-02-gap-e
#233AAV-PHP.eB-Mediated Microglial IGFBPL1 ExpressionIGFBPL10.720$0.72SDA-2026-04-06-gap-d
#234SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 RatioCXCL1, CXCL2, MMP30.720$0.72SDA-2026-04-06-gap-d
#235Microglial IFN-β Priming of Motor Neuron cGAS/STING AmplificationIFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)0.720$0.72SDA-2026-04-07-gap-p
#236ASO-Mediated Exon Skipping to Restore FUS-TAZ Chaperone AxisFUS0.720$0.70SDA-2026-04-14-gap-p
#237Antisense Oligonucleotide-Mediated APOE4 HaploinsufficiencyAPOE0.720$0.72SDA-2026-04-02-gap-a
#238Stress Granule Phase Separation ModulatorsG3BP10.720$0.67sda-2026-04-01-gap-v
#239Magnetosonic-Triggered Transferrin Receptor ClusteringTFR10.719$0.75sda-2026-04-01-gap-0
#240Retinal Vascular Microcirculation RescuePDGFRB/ANGPT10.718$0.74sda-2026-04-01-gap-0
#241Disease-Associated Microglia Metabolic ReprogrammingTREM20.718$0.67SDA-2026-04-03-gap-s
#242TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial Metabolic FitnessTREM2, TYROBP, SYK, PI3K0.718$0.70SDA-2026-04-02-gap-0
#243APOE Isoform Conversion TherapyAPOE0.718$0.75sda-2026-04-01-gap-a
#244Engineered Apolipoprotein E4-Neutralizing Shuttle PeptidesAPOE, LRP1, LDLR0.718$0.74sda-2026-04-01-gap-0
#245C9orf72 DPRs Impair Autophagy Receptor Docking on Stress GranulesC9orf72, p62/SQSTM1, OPTN0.717$0.72SDA-2026-04-06-gap-p
#246Vascular-Glial Interface RestorationCLDN50.716$0.74SDA-2026-04-03-gap-s
#247Circadian-Synchronized LRP1 Pathway ActivationLRP1, MTNR1A, MTNR1B0.714$0.74sda-2026-04-01-gap-0
#248Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from InflammationTREM2, ADAM10, ADAM170.714$0.70SDA-2026-04-02-gap-0
#249Purinergic Signaling Polarization ControlP2RY1 and P2RX70.713$0.73sda-2026-04-01-gap-0
#250Test: TREM2 enhances amyloid clearance-0.712$0.70-
#251Circadian Glymphatic Rescue Therapy (Melatonin-focused)MTNR1A0.712$0.74sda-2026-04-01-gap-v
#252Early Proteasome Restoration TherapyPSMC0.712$0.66SDA-2026-04-03-gap-a
#253Noradrenergic-Tau Propagation BlockadeADRA2A0.711$0.74sda-2026-04-01-gap-v
#254APOE4-Specific Microglial Metabolic RescueAPOE, ABCA1, LDLR0.710$0.74SDA-2026-04-04-gap-n
#255HDAC3-Selective Inhibition for Clock ResetHDAC30.710$0.74sda-2026-04-01-gap-v
#256CSF YKL-40 as a Priming-Specific Chitinase MarkerCHI3L1/YKL-400.710$0.71SDA-2026-04-06-gap-d
#257Microglial Disease-Associated States: TREM2-Independent Pathways Driving NeuroinflammationAPOE0.710$0.71SDA-2026-04-02-gap-s
#258H4: Senomorphic Compounds Preserve Astrocyte Function While Reversing SenescenceMTOR; MEGF10; MERTK0.710$0.71SDA-2026-04-06-gap-d
#259Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes, normalizing cholesterol export and reducing AD-relevant neurotoxicityNR1H2 (LXRβ), ABCA1, ABCG10.710$0.71SDA-2026-04-04-gap-a
#260p21^Cip1 Phospho-State as Autophagy Responsiveness PredictorCDKN1A, CDK4, CDK6, ATM, PPP1CA0.710$0.71SDA-2026-04-07-gap-d
#261Conformational-Selective Blocking of Tau Uptake Reveals Therapeutic Window in Neuronal Re-entryLRP1, HSPG (SDC3, GPC1), tau conformations0.710$0.71SDA-2026-04-06-gap-d
#262Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in Alzheimer's DiseaseTREM20.710$0.71SDA-2026-04-06-gap-p
#263Liquid-to-Solid Transition Pathology Reveals Granule Weak PointsTDP-43, FUS, TIA1, G3BP10.710$0.71SDA-2026-04-07-gap-p
#264Metabolic Circuit Breaker via Lipid Droplet ModulationPLIN20.709$0.74sda-2026-04-01-gap-0
#265Autophagosome Maturation Checkpoint ControlSTX170.709$0.74sda-2026-04-01-gap-0
#266Matrix Stiffness Normalization via Targeted Lysyl Oxidase InhibitionLOX/LOXL1-40.709$0.73sda-2026-04-01-gap-v
#267TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to RestorativeTREM20.708$0.71SDA-2026-04-07-gap-p
#268Membrane Cholesterol Gradient ModulatorsABCA1/LDLR/SREBF20.708$0.73SDA-2026-04-01-gap-l
#269Orexin-Microglia Modulation TherapyHCRTR20.707$0.74sda-2026-04-01-gap-v
#270Creatine Kinase System Capacity as Neural Energy Reserve BiomarkerCKB0.707$0.70SDA-2026-04-04-gap-d
#271TET2-Mediated Demethylation Rejuvenation TherapyTET20.706$0.73sda-2026-04-01-gap-v
#272Autophagy-Lysosomal Degradation of IBA1 in Stressed MicrogliaLC3/P62/SQSTM10.706$0.71SDA-2026-04-07-gap-p
#273Lysosomal Enzyme Trafficking CorrectionIGF2R0.706$0.73sda-2026-04-01-gap-0
#274Endothelial Glycocalyx Regeneration via Syndecan-1 UpregulationSDC10.705$0.73sda-2026-04-01-gap-v
#275Spatiotemporal coupling between TRPML1-mediated lysosomal calcium release and calcineurin nanodomain activationTRPML1/MCOLN10.705$0.70SDA-2026-04-07-gap-p
#276Test: TREM2 enhances amyloid clearance-0.705$0.70-
#277Ferroptosis Inhibition for α-Synuclein NeuroprotectionGPX40.705$0.73SDA-2026-04-03-gap-a
#278Microglial Efferocytosis Enhancement via GPR32 SuperagonistsCMKLR10.704$0.73sda-2026-04-01-gap-0
#279Astrocyte-Neuron Metabolic Coupling TitrationBDH10.704$0.70SDA-2026-04-03-gap-d
#280Multiplexed Base Editing for Simultaneous Neuroprotective Gene ActivationSOD1, TARDBP, BDNF, GDNF, IGF-10.704$0.74SDA-2026-04-03-gap-c
#281TLR4/MyD88/NF-κB Axis Blockade to Interrupt LPS-Mediated Gut-Brain Neuroinflammation in PDTLR4, MyD88 (MYD88), NF-κB (NFKB1)0.703$0.73SDA-2026-04-16-gap-2
#282Purinergic P2Y12 Inverse Agonist TherapyP2RY120.703$0.73sda-2026-04-01-gap-v
#283Microglial Exosome-Mediated Tau PropagationMAPT0.702$0.67SDA-2026-04-03-26abc
#284Mitochondrial-Nuclear Epigenetic Cross-Talk RestorationSIRT30.701$0.73SDA-2026-04-04-gap-e
#285DAMP-Scavenging Microglial ResetHMGB1, S100 proteins0.701$0.73SDA-2026-04-04-gap-n
#286Microglial Purinergic ReprogrammingP2RY120.701$0.73sda-2026-04-01-gap-0
#287Transglutaminase-2 Cross-Linking Inhibition StrategyTGM20.701$0.73sda-2026-04-01-gap-9
#288Targeted Butyrate Supplementation for Microglial Phenotype ModulationGPR109A0.700$0.73SDA-2026-04-01-gap-2
#289NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward SenescenceSIRT1/NAMPT/PPARGC1A0.700$0.70SDA-2026-04-06-gap-p
#290Metabolic Coupling Disruption Sensitizes Motor Neuron mPTP ThresholdPDH (pyruvate dehydrogenase), MCT1/2, PDK, mPTP (ANT/VDAC/Cyclophilin D)0.700$0.70SDA-2026-04-07-gap-p
#291TRIM21 as a 'Phase Separation Thermostat' via Catalytic ReversibilityTRIM210.700$0.70SDA-2026-04-07-gap-p
#292FOXO3-Pioneer Factor Complex Stabilizes Heterochromatin Under Oxidative StressFOXO3; SIRT10.700$0.70SDA-2026-04-10-gap-2
#293SCFA-Producing Bacterial Depletion → Loss of Neuroprotective MicroenvironmentHDAC3, GPR41 (FFAR3), GPR43 (FFAR2), Nrf2, HMOX10.700$0.70sda-2026-04-01-gap-2
#294Ataxin-2 Polyglutamine Expansions Hijack G3BP1 to Form Toxic, Irreversible Stress Granule ComplexesATXN20.700$0.70SDA-2026-04-06-gap-p
#295TREM2 haploinsufficiency dysregulates microglial synaptic surveillance, switching from protective 'disease-associated microglia' to neurotoxic 'inflammasome-active' statesTREM2, TYROBP (DAP12), APOE0.700$0.70SDA-2026-04-02-gap-s
#296m6A RNA Modification as Address Code for Granule TargetingMETTL3, METTL14, FTO, ALKBH5, YTHDF1, YTHDF2, YTHDC10.700$0.70SDA-2026-04-07-gap-p
#297AAV-Mediated APOE2/APOE3 Gene Delivery to Convert APOE GenotypeAPOE0.700$0.70SDA-2026-04-02-gap-a
#298Mechanosensitive Ion Channel ReprogrammingPIEZO1 and KCNK20.700$0.72sda-2026-04-01-gap-0
#299TREM2-Mediated Selective Aggregate Clearance PathwayTREM20.699$0.73sda-2026-04-01-gap-9
#300H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective EffectorPXR (NR1I2), IDO10.699$0.70SDA-2026-04-15-gap-p
#301Granzyme B Inhibition with Serpina3n to Preserve Axonal Integrity Against Cytotoxic AttackGZMB0.698$0.73SDA-2026-04-15-gap-d
#302H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate PropertiesC9orf72, G3BP10.698$0.70SDA-2026-04-06-gap-p
#303SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-Dependent Axon DegenerationSARM1, NMNAT20.698$0.69SDA-2026-04-13-gap-p
#304TFEB-Independent Autophagy BypassULK10.697$0.65SDA-2026-04-03-gap-d
#305Lysosomal Calcium Channel Modulation TherapyMCOLN10.697$0.73sda-2026-04-01-gap-0
#306Perforant Path Presynaptic Terminal Protection StrategyPPARGC1A0.696$0.72sda-2026-04-01-gap-0
#307Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated AmplificationMAPT0.696$0.73SDA-2026-04-03-26abc
#308Axonal RNA Transport ReconstitutionHNRNPA2B10.695$0.73sda-2026-04-01-gap-v
#309Mitochondrial Transfer Pathway EnhancementMIRO10.695$0.73sda-2026-04-01-gap-0
#310Temporal Microglial State SwitchingOptogenetic constructs, ion channels0.695$0.73SDA-2026-04-04-gap-n
#311Complement C1q Mimetic Decoy TherapyC1QA0.695$0.72sda-2026-04-01-gap-v
#312Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene TherapyALOX150.695$0.72sda-2026-04-01-gap-0
#313Palmitoylation-Targeted BACE1 Trafficking DisruptorsBACE10.693$0.73SDA-2026-04-01-gap-l
#314Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial LossCCR20.693$0.69SDA-2026-04-07-gap-p
#315Drp1-S616 Phosphorylation Fission Priming Enables t-Bid-Driven MPTP AmplificationDRP1 (DNM1L), BID0.693$0.69SDA-2026-04-08-gap-p
#316Astrocytic Connexin-43 Upregulation Enhances Neuroprotective Mitochondrial DonationGJA10.692$0.72sda-2026-04-01-gap-2
#317Ocular Immune Privilege ExtensionFOXP3/TGFB10.692$0.72sda-2026-04-01-gap-0
#318Sphingomyelin Synthase Activators for Raft RemodelingSGMS1/SGMS20.692$0.72SDA-2026-04-01-gap-l
#319TREM2-Mediated Microglial Dysfunction Disrupts Oligodendrocyte Tau Clearance NetworksTREM20.691$0.74SDA-2026-04-03-26abc
#320TREM2-Dependent Microglial Surveillance Controls AQP4-Mediated Tau Clearance Through Astrocytic Endfoot MaintenanceTREM20.691$0.74SDA-2026-04-03-26abc
#321cGAS-STING Senescence Circuit DisruptionCGAS, STING10.691$0.72SDA-2026-04-03-gap-a
#322Extracellular Matrix Stiffness ModulationPIEZO10.691$0.72sda-2026-04-01-gap-0
#323Epigenetic Memory Reprogramming via CRISPRa-Mediated Chromatin RemodelingSIRT1, FOXO3, NRF2, TFAM0.690$0.72SDA-2026-04-03-gap-c
#324Time-Limited AQP4 Inhibition for Acute Cytotoxic Edema Followed by Therapeutic ReleaseAQP40.690$0.69SDA-2026-04-07-gap-p
#325H5: BET Bromodomain Readers Sense Aberrant Chromatin and Drive Neuroinflammatory TranscriptionBRD4, BET bromodomains (BRD2/3/4)0.690$0.69SDA-2026-04-04-gap-2
#326TFEB-Dependent Lysosome BiogenesisTFEB/TFE30.690$0.69SDA-2026-04-07-gap-p
#327Rab27A/B-mediated exosomal tau secretion from microglia drives frontal cortex propagation at Braak III-VIRAB27A0.690$0.69SDA-2026-04-07-gap-d
#328TREM2 Agonism to Rescue APOE4-Induced Microglial DysfunctionTREM20.690$0.69SDA-2026-04-02-gap-a
#329Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GRNGRN, SLC16A3 (MCT4)0.690$0.69SDA-2026-04-02-gap-2
#330Loss of AQP4 Polarization Impairs Glymphatic Perivascular Influx, Causing Metabolite AccumulationAQP40.690$0.69SDA-2026-04-07-gap-p
#331Astrocyte Reactivity Heterogeneity with APOE4-Dependent VulnerabilityAPOE0.690$0.69SDA-2026-04-02-gap-s
#332TREM2-Dependent Microglial State Transition as Therapeutic Window in Alzheimer's DiseaseTREM2, SYK signaling pathway0.690$0.69SDA-2026-04-02-gap-2
#333Ganglioside Rebalancing TherapyST3GAL2/ST8SIA10.690$0.72SDA-2026-04-01-gap-l
#334Endothelial NRF2 Activation as a Master Switch for Post-CA BBB ProtectionNRF2 (NFE2L2) in brain microvascular endothelial cells0.689$0.81SDA-2026-04-16-gap-p
#335Reelin-Mediated Cytoskeletal Stabilization ProtocolRELN0.689$0.72sda-2026-04-01-gap-0
#336Cross-Seeding Prevention StrategyTARDBP0.689$0.72sda-2026-04-01-gap-v
#337Hypocretin-Neurogenesis Coupling TherapyHCRT0.688$0.72sda-2026-04-01-gap-v
#338Lysosomal Positioning Dynamics ModulationLAMP10.686$0.72sda-2026-04-01-gap-0
#339Wnt/β-catenin Pathway RestorationCTNNB10.686$0.72SDA-2026-04-16-gap-b
#340CX43 hemichannel engineering enables size-selective mitochondrial transferGJA10.686$0.72sda-2026-04-01-gap-v
#341TREM2 Conformational Stabilizers for Synaptic DiscriminationTREM20.685$0.72sda-2026-04-01-gap-v
#342mTORC1 Reactivation as Autophagy-Senescence Divergence Point MarkerMTOR, RPTOR, RPS6KB1, TSC1, TSC20.685$0.69SDA-2026-04-07-gap-d
#343GLUT1-Mediated Glucose Flux Coefficient as Neuroprotection IndicatorSLC2A10.685$0.69SDA-2026-04-04-gap-d
#344Pericyte Contractility Reset via Selective PDGFR-β AgonismPDGFRB0.684$0.72sda-2026-04-01-gap-v
#345hnRNPA2B1-Mediated Structural Remodeling Controls lncRNA-0021 Accessibility for miR-6361 SequestrationhnRNPA2B1, lncRNA-0021 (RBP-bound state)0.684$0.65SDA-2026-04-16-gap-p
#346Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance FateAHR, IL10, TNFRSF13B, TIGIT, FOXP30.683$0.68SDA-2026-04-13-gap-p
#347Multi-Target Synergy via Presynaptic Vesicle Hub ConvergenceTH, VMAT2, DAT, GCH1, BDNF, SNCA (presynaptic hub)0.683$0.67SDA-2026-04-13-gap-p
#348STMN2 Restoration as a Prerequisite for Axon Growth After TDP-43 ClearanceSTMN20.683$0.71SDA-2026-04-14-gap-p
#349Astrocyte-Selective APOE4 Silencing via Lipid NanoparticlesAPOE40.682$0.70SDA-2026-04-03-gap-d
#350Context-Dependent CRISPR Activation in Specific Neuronal SubtypesCell-type-specific essential genes0.682$0.71SDA-2026-04-03-gap-c
#351Differential Ubiquitin Chain Topology Creates 'Invisible' Surface on Pathological Stress GranulesTRIM21, G3BP1, OTUD1/OTUD7B0.682$0.68SDA-2026-04-06-gap-p
#352HDAC6 Activation as SCFA-Mediated Neuroprotective MechanismHDAC6, HSP90AA10.682$0.72SDA-2026-04-12-gap-d
#353Temporal CAG Repeat Stabilization via CRISPR-Mediated DNA Mismatch Repair ModulationMSH3, PMS10.681$0.64SDA-2026-04-03-gap-c
#354Flotillin-1 Stabilization CompoundsFLOT10.681$0.71SDA-2026-04-01-gap-l
#355Interneuron SYNGAP1 Deficiency Disrupts Cortical Circuit Assembly During DevelopmentSYNGAP10.681$0.67SDA-2026-04-15-gap-p
#356CRISPR-Mediated Mitochondrial Genome Editing for Complex I DysfunctionMT-ND1, MT-ND4, MT-ND60.681$0.72SDA-2026-04-03-gap-c
#357R-Loop Resolution Enhancement TherapySETX0.680$0.71sda-2026-04-01-gap-v
#358Chaperone-Mediated APOE4 Refolding EnhancementHSPA1A, HSP90AA1, DNAJB1, FKBP50.680$0.70sda-2026-04-01-gap-0
#359Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid PlexusAQP10.680$0.71sda-2026-04-01-gap-v
#360Oligodendrocyte Protectin D1 Mimetic for Myelin ResolutionGPR370.680$0.71sda-2026-04-01-gap-0
#361GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis BlockadeGPX40.680$0.65SDA-2026-04-16-gap-f
#362Pharmacological EZH2 Inhibition Resets Polycomb-Mediated Repression of Synaptic Transmission Genes in 3xTg-AD NeuronsEZH2/H3K27me30.680$0.68SDA-2026-04-04-gap-2
#363LRP1-Mediated Transcytosis for CNS Antibody DeliveryLRP1 (LRP1 gene); clathrin-mediated endocytosis pathway0.680$0.68SDA-2026-04-02-gap-b
#364AQP4 Dysregulation Promotes Neuroinflammation Through Impaired CNS-Peripheral Immune Interface FunctionAQP4; IL6R; CD46 (complement)0.680$0.68SDA-2026-04-07-gap-p
#365Synaptic Phosphatidylserine Masking via Annexin A1 MimeticsANXA10.680$0.71sda-2026-04-01-gap-v
#366CSF Soluble TREM2 Fragment Ratio as Priming State IndicatorTREM2/ADAM10/170.680$0.68SDA-2026-04-06-gap-d
#367Glial Neuroinflammatory Amplification by TDP-43 PathologyTARDBP0.680$0.68SDA-2026-04-08-gap-p
#368Bacterial Tyramine–Induced DOPAL Accumulation in Enteric NeuronsTyrDC (bacterial), ALDH1A1, MAOB, SLC6A3 (DAT)0.680$0.68sda-2026-04-01-gap-2
#369TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic strategy for ADTFEB (TFEC)0.680$0.68SDA-2026-04-04-gap-l
#370Complement C1QA Spatial Gradient in Cortical LayersC1QA0.678$0.70analysis-SEAAD-20260
#371Dynamic Lactate-Pyruvate Ratio as Therapeutic Stratification BiomarkerSLC16A10.677$0.67SDA-2026-04-04-gap-d
#372Cell-Type Specific TFEB ModulationTFEB0.677$0.70SDA-2026-04-03-gap-d
#373Astrocyte-Mediated Microglial Memory ErasureGFAP, S100B0.677$0.71SDA-2026-04-04-gap-n
#374Microglial TREM2-Mediated Tau Phagocytosis ImpairmentMAPT0.676$0.72SDA-2026-04-03-26abc
#375Selective Tau Kinase Inhibition in Vulnerable Neuronal SubtypesMAPT0.676$0.71SDA-2026-04-03-gap-s
#376White Matter Oligodendrocyte Protection via CXCL10 InhibitionCXCL100.675$0.70SDA-2026-04-03-gap-a
#377Excitatory Neuron Vulnerability via SLC17A7 DownregulationSLC17A70.675$0.70analysis-SEAAD-20260
#378RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo deliveryRAB27A0.674$0.71sda-2026-04-01-gap-v
#379Metabolic Reprogramming via Microglial Glycolysis InhibitionHK20.672$0.71sda-2026-04-01-gap-v
#380Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.672$0.72SDA-2026-04-03-26abc
#381FOXO3-Longevity Pathway Epigenetic ReprogrammingFOXO30.672$0.71sda-2026-04-01-gap-v
#382TREM2 R47H Metabolic Lock-in at Cholesterol Ester AccumulationTREM2/ACAT1/LXR0.672$0.70SDA-2026-04-15-gap-d
#383Partial Neuronal Reprogramming via Modified Yamanaka CocktailOCT40.672$0.70SDA-2026-04-04-gap-e
#384Age-Dependent Complement C4b Upregulation Drives Synaptic Vulnerability in Hippocampal CA1 NeuronsC4B0.671$0.70SDA-2026-04-03-gap-a
#385AQP4-Dependent Astrocyte Swelling Exacerbates Excitotoxic Neuronal Death via Dysfunction of the Glutamate-Gln CycleAQP4; SLC1A2 (GLT-1)0.670$0.67SDA-2026-04-07-gap-p
#386Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased AgonismFFAR2, FFAR3, NLRP30.670$0.70SDA-2026-04-12-gap-d
#387OPTN/TBK1 mutations create selective vulnerability by blocking PINK1-Parkin-independent mitophagy in lower motor neuronsOPTN0.670$0.67SDA-2026-04-08-gap-p
#388H1: TET-Mediated 5-Hydroxymethylcytosine Loss Drives Neuronal Transcriptomic DriftTET1, TET2, 5-hydroxymethylcytosine (5hmC)0.670$0.67SDA-2026-04-04-gap-2
#389Microglial P2Y12-Dependent Territorial Segregation of Synaptic InputsP2RY12 (P2Y12 receptor)0.670$0.67SDA-2026-04-07-gap-p
#390Restore AQP4 Perivascular Polarization by Stabilizing DAPC/SNTA1/DAG1 Anchoring ComplexAQP4, SNTA1, DAG10.670$0.67SDA-2026-04-07-gap-p
#391LPS-primed microglial trained immunity establishes persistent H3K4me3 landscapes at complement gene loci, driving hyperactive synaptic pruning in late-life neurodegenerationNLRP3, H3K4me3 writers (MLL3/4, SETD1A), H3K27ac (EP300/CREBBP)0.670$0.67SDA-2026-04-02-gap-s
#392TREM2 R47H variant synergizes with APOE4 to collapse microglial lipid clearance capacity, causing extracellular lipid accumulation that feeds back to astrocyte lipid droplet formationTREM2, APOE0.670$0.67SDA-2026-04-04-gap-a
#393Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory CommunicationCHRNA70.669$0.70SDA-2026-04-01-gap-2
#394Astrocyte MCT1/MCT4 Ratio Disruption with Metabolic UncouplingSLC16A10.668$0.70SDA-2026-04-03-gap-s
#395Heat Shock Protein 70 Disaggregase AmplificationHSPA1A0.668$0.70sda-2026-04-01-gap-0
#396TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition CheckpointTREM2, SYK signaling axis0.668$0.67SDA-2026-04-06-gap-d
#397Aquaporin-4 Polarization Enhancement via TREK-1 Channel ModulationKCNK20.668$0.70sda-2026-04-01-gap-v
#398Mitochondrial-Lysosomal Contact Site EngineeringRAB7A0.668$0.70sda-2026-04-01-gap-0
#399SIRT6-NAD+ Axis Enhancement TherapySIRT60.667$0.70sda-2026-04-01-gap-v
#400White Matter Vulnerability Prevention via Oligodendrocyte ProtectionCXCL100.667$0.70SDA-2026-04-03-gap-a
#401Lipid Droplet Dynamics as Phenotype SwitchesDGAT1 and SOAT10.666$0.70sda-2026-04-01-gap-0
#402LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Suppression-0.666$0.70SDA-2026-04-16-gap-p
#403Glymphatic-Cholinergic Tau Clearance CascadeMAPT0.666$0.70SDA-2026-04-03-26abc
#404GAP43-mediated tunneling nanotube stabilization enhances neuroprotective mitochondrial transferGAP430.666$0.70sda-2026-04-01-gap-v
#405Lactate/Pyruvate Ratio Dynamics in CSF as a Neuroinflammation-Metabolism Interface BiomarkerLDHA, TREM20.665$0.70SDA-2026-04-04-SDA-2
#406EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.665$0.70sda-2026-04-12-ev-ad
#407Oligodendrocyte DNA Repair Enhancement TherapyPARP1 and XRCC10.665$0.70SDA-2026-04-03-gap-s
#408Complement C1q Subtype SwitchingC1QA0.665$0.70sda-2026-04-01-gap-0
#409Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD SpectrumSTMN2 (stathmin-2), PTBP1/PTBP20.664$0.65SDA-2026-04-13-gap-2
#410Gut Barrier Permeability-α-Synuclein Axis ModulationCLDN1, OCLN, ZO1, MLCK0.663$0.69SDA-2026-04-01-gap-2
#411TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between SASP and Synaptic PruningTNF, IL1B → GJA1 → C1Q/C30.663$0.70SDA-2026-04-12-gap-d
#412Sphingolipid Metabolism ReprogrammingCERS20.663$0.70sda-2026-04-01-gap-0
#413Choline Kinase Activity as Membrane Integrity Response IndicatorCHKA0.663$0.65SDA-2026-04-04-gap-d
#414RNA Granule Nucleation Site ModulationG3BP10.662$0.70sda-2026-04-01-gap-0
#415Peripheral-Central Immune Decoupling TherapyTREM2, complement cascade components0.662$0.69SDA-2026-04-04-gap-n
#416Circadian-Metabolic Microglial ReprogrammingCLOCK, BMAL1, PER20.662$0.69SDA-2026-04-04-gap-n
#417EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.661$0.71sda-2026-04-12-ev-ad
#418PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 ActivationPARP10.661$0.65SDA-2026-04-15-gap-p
#419Biorhythmic Interference via Controlled Sleep OscillationsGABRA10.661$0.70sda-2026-04-01-gap-0
#420Axonal Transport Defect: C9orf72 hexanucleotide expansion impairs retrograde autophagosome transport in motor neuron axonsC9orf720.660$0.66SDA-2026-04-08-gap-p
#421BBB Integrity Loss Defines Absolute Therapeutic Window ClosureMMP-9, Claudin-5, PDGFRβ (pericyte coverage)0.660$0.66SDA-2026-04-06-gap-d
#422Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I Interferon SignalingcGAS (CGAS) / STING (TMEM173) / IFNAR1/20.660$0.66SDA-2026-04-07-gap-p
#423Astrocyte IL-1β as Paracrine Mediator of Microglial Complement ExpressionIL1B; IL1R1; MYD880.660$0.66SDA-2026-04-08-gap-p
#424Focused Ultrasound with Microbubble Contrast AgentsIGFBPL10.660$0.66SDA-2026-04-06-gap-d
#425H6: miR-132/212 Cluster Silencing Disables Neuronal Chromatin Compaction and SurvivalmiR-132-3p, MeCP2, DNMT3A0.660$0.66SDA-2026-04-04-gap-2
#426Vagal Afferent Microbial Signal ModulationGLP1R, BDNF0.660$0.69SDA-2026-04-01-gap-2
#427Complement C1QA Inhibition Synergizes with PV Interneuron ModulationC1QA, PVALB0.659$0.65SDA-2026-04-13-gap-p
#428NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP AmplificationNLRP30.657$0.69SDA-2026-04-12-gap-d
#429TREM2 Activation as an Amplification Node for R136S ProtectionTREM20.657$0.65SDA-2026-04-13-gap-p
#430Temporal TET2-Mediated Hydroxymethylation CyclingTET20.657$0.70SDA-2026-04-04-gap-e
#431Liquid-Liquid Phase Separation Modifier TherapyG3BP10.656$0.69sda-2026-04-01-gap-9
#432Mitochondrial RNA Granule Rescue PathwaySYNCRIP0.656$0.69sda-2026-04-01-gap-v
#433Time-Dependent BBB Repair StrategyMULTIPLE0.656$0.70SDA-2026-04-16-gap-b
#434Cyclophilin D (CypD) Displacement by Mitochondrial TDP-43PPID (Cyclophilin D)0.656$0.66SDA-2026-04-08-gap-p
#435Parvalbumin Interneuron Vulnerability Links Lactate Transport to Gamma Oscillation DysfunctionPVALB, SLC16A1/MCT10.656$0.65SDA-2026-04-13-gap-p
#436Optogenetic Microglial Deactivation via Engineered Inhibitory OpsinsCX3CR10.655$0.70sda-2026-04-01-gap-v
#437Test: TREM2 enhances amyloid clearance-0.655$0.66-
#438Astrocyte-Microglia Communication Rebalancing via Cytokine ModulationIL1A, TNF, C1Q0.655$0.69SDA-2026-04-03-gap-d
#439Arginine Methylation Enhancement TherapyPRMT10.653$0.69sda-2026-04-01-gap-0
#440KDM6A-Mediated H3K27me3 RejuvenationKDM6A0.653$0.69sda-2026-04-01-gap-v
#441EPO Set Point Calibration Hypothesis-0.653$0.64SDA-2026-04-13-gap-p
#442GDF15-GFRAL Axis as Systemic Autophagy-Senescence IntegratorGDF15, GFRAL, NTRK20.653$0.65SDA-2026-04-07-gap-d
#443Nucleolar Stress Response NormalizationNPM10.653$0.69sda-2026-04-01-gap-v
#444Locus Coeruleus-Hippocampal Circuit ProtectionMAPT0.653$0.67SDA-2026-04-03-26abc
#445The Mitochondrial-Lysosomal Metabolic Coupling DysfunctionTFEB0.652$0.69SDA-2026-04-02-gap-v
#446SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and Links Synaptic Dysfunction to SASP-Complement ActivationSUMO1, SYT1, C1QA, C30.652$0.69SDA-2026-04-16-gap-d
#447Mitochondrial Biogenesis Rate as a Dynamic Biomarker of NeuroprotectionTFAM, MT-CO10.652$0.69SDA-2026-04-04-SDA-2
#448Microbiota-Microglia Axis ModulationMultiple0.651$0.68SDA-2026-04-04-gap-2
#449Oligodendrocyte White Matter VulnerabilityMOG0.651$0.69SDA-2026-04-03-gap-a
#450Astrocyte APOE4-Specific Lipid Metabolism CorrectionAPOE0.651$0.69SDA-2026-04-03-gap-s
#451Prohibitin-2 Mitochondrial Cross-Seeding Hub DisruptionPHB20.650$0.69sda-2026-04-01-gap-9
#452Mitochondrial Calcium Buffering Enhancement via MCU ModulationMCU0.650$0.69sda-2026-04-01-gap-0
#453Pharmacologically Boost AQP4X Readthrough to Restore Perivascular ClearanceAQP4, AQP4X0.650$0.65SDA-2026-04-07-gap-p
#454NeuroD1-Mediated Astrocyte Reprogramming Attenuates Neuroinflammation Through Epigenetic Remodeling of A1 Astrocyte Signature GenesNeuroD1/NF-kB0.650$0.65SDA-2026-04-04-gap-2
#455mTORC1 displacement from lysosomal surface enables calcineurin access to TFEBmTOR/FRAP10.650$0.65SDA-2026-04-07-gap-p
#456Galectin-3 deletion attenuates NLRP3 inflammasome activation downstream of lysosomal membrane permeabilizationLGALS30.650$0.65SDA-2026-04-04-gap-l
#457TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCsRELA (p65), IKBKB (IKKβ)0.650$0.65SDA-2026-04-07-gap-p
#458LDLR Ligand-Binding Domain A Fusion for Receptor-Mediated TranscytosisLDLR (LDLR gene); ARH/DAB2 adaptor proteins0.650$0.65SDA-2026-04-02-gap-b
#459NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Antioxidant DefenseNRF2 (NFE2L2), KEAP10.650$0.62SDA-2026-04-16-gap-f
#460Loss of Homeostatic Epigenetic Identity Reprograms Microglia to Dystrophic StateEZH2/DNMT1/DNMT3A/P2RY12/TMEM1190.650$0.65SDA-2026-04-06-gap-p
#461APOE-Mediated Synaptic Lipid Raft StabilizationSPTLC10.649$0.68sda-2026-04-01-gap-a
#462Glycosaminoglycan Template Disruption ApproachHSPG20.649$0.68sda-2026-04-01-gap-9
#463Glial Glycocalyx Remodeling TherapyHSPG20.649$0.69sda-2026-04-01-gap-0
#464Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading to Senescent Glial NetworksTREM20.649$0.64SDA-2026-04-03-gap-a
#465APOE-TREM2 Ligand Availability Dysfunction in NeurodegenerationAPOE0.649$0.64SDA-2026-04-03-gap-a
#466TREM2-Mediated Mitochondrial Dysfunction in NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#467p62 Liquid-Liquid Phase Separation Nucleates Cross-Organelle Cargo for Coordinated AutophagySQSTM1/p62 (SQSTM1), ULK1/FIP2000.649$0.65SDA-2026-04-07-gap-p
#468Apoptosis-Senescence Decision Point InterventionTP53,BAX,BAK1,CASP30.649$0.68SDA-2026-04-04-gap-s
#469TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling in White Matter NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#470IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage ReprogrammingIL10, CSF1R, CD400.648$0.65SDA-2026-04-13-gap-p
#471CLU-APOE-TREM2 Tripartite Axis as a Coordinate Therapeutic TargetCLU-APOE-TREM2 axis (LXR/RXR pathway)0.648$0.64SDA-2026-04-14-gap-p
#472ALS-Linked OPTN/TBK1 Mutations Impair Phosphorylation Cascade Required for Pathological SG RecognitionOPTN, TBK10.648$0.65SDA-2026-04-06-gap-p
#473DNMT1-Targeting Antisense Oligonucleotide ResetDNMT10.648$0.69sda-2026-04-01-gap-v
#474Mitochondrial SPM Synthesis Platform EngineeringALOX50.647$0.69sda-2026-04-01-gap-0
#475Epigenetic Reprogramming of Microglial MemoryDNMT3A, HDAC1/20.647$0.68SDA-2026-04-04-gap-2
#476Inflammatory State-Dependent Ketone TimingIRAKM0.647$0.64SDA-2026-04-03-gap-d
#477Grid Cell-Specific Metabolic Reprogramming via IDH2 EnhancementIDH20.646$0.69sda-2026-04-01-gap-0
#478Astrocyte Metabolic Memory ReprogrammingSIRT10.646$0.64SDA-2026-04-04-gap-d
#479NLRP3/Mitophagy Coupling ModulationNLRP30.646$0.67SDA-2026-04-03-gap-i
#480Synthetic Biology Rewiring via Orthogonal ReceptorsCNO0.645$0.69sda-2026-04-01-gap-0
#481Miro1-Mediated Mitochondrial Trafficking Enhancement TherapyRHOT10.645$0.68sda-2026-04-01-gap-2
#482Ephrin-B2/EphB4 Axis ManipulationEPHB40.645$0.68sda-2026-04-01-gap-0
#483Oligodendrocyte Remyelination EnhancementTREM20.644$0.67SDA-2026-04-03-gap-a
#484Temporal Metabolic Window TherapyHMGCS20.644$0.63SDA-2026-04-04-gap-d
#485MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM DysfunctionMFN2, GRP75 (HSPA9), MCU (MICU1/2)0.644$0.64SDA-2026-04-08-gap-p
#486Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy-0.644$0.63SDA-2026-04-15-gap-p
#487White Matter Immune Checkpoint RestorationCXCL100.644$0.68SDA-2026-04-03-gap-a
#488Epigenetic Silencing of AIF1 Gene Locus by Chronic InflammationDNMT1/DNMT3A0.643$0.64SDA-2026-04-07-gap-p
#489HDAC2 Phospho-Lock Window for Synaptic Gene SilencingHDAC2 (phospho-S421)0.643$0.64SDA-2026-04-07-gap-d
#490Cell-Type Specific Metabolic ReprogrammingPPARA0.643$0.68SDA-2026-04-03-gap-s
#491HDAC6 Selective Inhibition to Restore Acetylation Balance and Microtubule StabilityHDAC60.643$0.63SDA-2026-04-13-gap-d
#492Mitochondrial ATP/ADP Carrier Activity as Bioenergetic Recovery MetricSLC25A40.642$0.67SDA-2026-04-04-gap-d
#493TREM2-Driven Senescence Biomarker Index for Predicting Neurodegeneration RiskTREM20.642$0.64SDA-2026-04-03-gap-a
#494Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-SeedingCSGA0.642$0.68SDA-2026-04-01-gap-2
#495RNA-Binding Competition Therapy for TDP-43 Cross-SeedingTARDBP0.642$0.68sda-2026-04-01-gap-9
#496Glycine-Rich Domain Competitive InhibitionTARDBP0.640$0.68sda-2026-04-01-gap-0
#497H7: mTOR Hyperactivity Blocks Autophagy, Permitting Tau SeedingMTOR, ULK1, TFG0.640$0.64SDA-2026-04-02-gap-e
#498Neuronal TET1 Upregulation Reactivates Immediate-Early Genes and Restores Dendritic Spine Plasticity via Active DNA DemethylationTET1/5hmC0.640$0.64SDA-2026-04-04-gap-2
#499Autophagic Flux Enhancement Synergizes With Chaperones to Clear High-Molecular-Weight Tau SeedsTFEB, LAMP2A, SQSTM10.640$0.64SDA-2026-04-06-gap-d
#500Colonic Th17/IL-17A Axis → Peripheral Immune Recruitment to SN and Neuronal ApoptosisRORC (RORγt), IL17A, IL17RA, IL17RC, CXCL9, CXCL10, CXCR3, CD8A0.640$0.64sda-2026-04-01-gap-2
#501Small Molecule Modulation of Phase SeparationFUS, TDP-43, G3BP10.640$0.64SDA-2026-04-07-gap-p
#502C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque MacrophagesC1QA/C1QC0.640$0.64SDA-2026-04-07-gap-p
#503Critical Period Hypothesis: The Therapeutic Window Closes When Neuronal Homeostasis is Irreversibly DisruptedNfL, p-tau217, p-tau231, ATF4, TOMM400.640$0.64SDA-2026-04-06-gap-d
#504CDK5 Inhibition at Presynaptic Terminals Prevents Activity-Dependent Tau Release and Transsynaptic PropagationCDK50.640$0.64SDA-2026-04-04-gap-2
#505CX3CR1 Promoter Methylation Disrupts Neuron-Microglia Cross-TalkCX3CR10.640$0.64SDA-2026-04-07-gap-d
#506Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progressionGFAP0.640$0.68SDA-2026-04-04-analy
#507Mitochondrial NAD+ Salvage EnhancementSTING10.639$0.67SDA-2026-04-03-gap-a
#508Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelopmental FormsSOD1, HTT, TARDBP0.638$0.67SDA-2026-04-03-gap-c
#509Selective Neuronal Vulnerability Network TargetingCell-type specific vulnerability markers0.638$0.67SDA-2026-04-03-gap-a
#510Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid PhaseTREM20.637$0.62SDA-2026-04-02-gap-0
#511Test: TREM2 enhances amyloid clearance-0.637$0.64-
#512H1: CK2 Hyperphosphorylation Locks G3BP1 in Hyper-condensed StateCSNK2A1/CSNK2B, G3BP10.637$0.64SDA-2026-04-06-gap-p
#513Vascular mural cell degeneration precedes and exacerbates parenchymal pathologyPDGFRB0.637$0.66SDA-2026-04-04-analy
#514Astrocyte Metabolic Reprogramming via APOE4 CorrectionAPOE0.636$0.67SDA-2026-04-03-gap-s
#515TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection FilterTREM20.636$0.62SDA-2026-04-15-gap-d
#516ER-Mitochondria Calcium Microdomains Couple Mitophagy and ER-Phagy InitiationITPR1 (IP3R1), VDAC1, MCU0.636$0.64SDA-2026-04-07-gap-p
#517HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.634$0.68SDA-2026-04-04-gap-t
#518DLK MAPK Pathway Inhibition to Block Tau-Induced Neurotoxicity Without Directly Targeting TauMAP2K7/MAP3K120.634$0.67SDA-2026-04-15-gap-p
#519C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic LoopC3AR1, C3, NFKB10.633$0.65SDA-2026-04-14-gap-p
#520G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autophagy ReceptorsG3BP10.633$0.63SDA-2026-04-08-gap-p
#521Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1STAT3/JAK10.633$0.63SDA-2026-04-07-gap-p
#522HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding InhibitorDNAJB60.632$0.67sda-2026-04-01-gap-9
#523Layer V excitatory neurons show selectively enhanced vulnerability through dysregulated calcium signalingSLC17A70.632$0.65SDA-2026-04-04-analy
#524TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk AlleleTREM20.631$0.61SDA-2026-04-02-gap-0
#525Gap Junction Hemichannel Modulation for Controlled Mitochondrial ExchangePANX10.631$0.67sda-2026-04-01-gap-2
#526CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Preventing Template-Dependent MisfoldingCX3CR10.630$0.63SDA-2026-04-04-gap-2
#527Intestinal Permeability Defects → Systemic LPS Translocation → Microglial PrimingTight junction complex (CLDN1, OCLN, TJP1), LBP, CD14, TLR4, MYD88, NFKB10.630$0.63sda-2026-04-01-gap-2
#528Epigenetic Bivalency at CDKN2A Locus Distinguishes Senescent from Activated MicrogliaCDKN2A, H3K9me3, DREAM complex (LIN9, LIN37, RBL2)0.630$0.63SDA-2026-04-06-gap-d
#529Hierarchical Phase Separation with Scaffold CoresDdx6, 4E-T, FMRP, TIA1, G3BP10.630$0.63SDA-2026-04-07-gap-p
#530Steric Occlusion of G3BP1 Oligomerization InterfaceG3BP10.630$0.63SDA-2026-04-07-gap-p
#531Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoot Repair in NMOSDAQP4, IL6R, CD19, C50.630$0.63SDA-2026-04-07-gap-p
#532Restoration of V-ATPase function reverses lysosomal acidification defect in AD neuronsATP6V1A, ATP6V0C0.630$0.63SDA-2026-04-04-gap-l
#533Partial OSK Reprogramming Reverses Epigenetic Aging Without DedifferentiationOct4; Sox2; Klf4; TP530.630$0.63SDA-2026-04-10-gap-2
#534Targeting Synaptic Vesicle Release Machinery to Block Tau ExocytosisSNAP250.630$0.63SDA-2026-04-04-gap-t
#535Autophagosome-Lysosome Fusion Defects as Primary Driver of α-Synuclein PropagationVPS41, STX17, HOPS complex, TRPML1 (MCOLN1)0.630$0.63SDA-2026-04-02-gap-2
#536Treat Glymphatic Failure by Coupling AQP4-Targeted Therapy to Sleep/Noradrenergic StateAQP4, ADRA2, LC0.630$0.63SDA-2026-04-07-gap-p
#537Selective Cholinergic Protection via APP Pathway ModulationAPP0.629$0.66SDA-2026-04-03-gap-a
#538APOE4-Driven Astrocyte Senescence as Primary TargetAPOE,CDKN1A,BCL2L10.629$0.66SDA-2026-04-04-gap-s
#539Gut-Brain Axis M-Cell ModulationGP2, SPIB0.629$0.66SDA-2026-04-04-gap-n
#540TREM2 Antagonism in Late-Stage Tauopathy — Reducing Neuroinflammatory AmplificationTREM20.628$0.61SDA-2026-04-02-gap-0
#541Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's diseaseTREM20.628$0.67SDA-2026-04-04-analy
#542Quantum Coherence Disruption in Cellular CommunicationTUBB30.627$0.69sda-2026-04-01-gap-0
#543Synthetic Biology Approach: Designer Mitochondrial Export SystemsSynthetic fusion proteins0.627$0.67sda-2026-04-01-gap-2
#544Cardiovascular-Neuroinflammatory Dual TargetingTNF/IL60.627$0.66SDA-2026-04-04-gap-2
#545TREM2 Super-Agonist Induction of DAM Program-0.627$0.63SDA-2026-04-16-gap-2
#546Default Mode Network Circuit StabilizationVIP0.627$0.66SDA-2026-04-03-26abc
#547Microbial Metabolite-Mediated α-Synuclein DisaggregationSNCA, HSPA1A, DNMT10.626$0.67SDA-2026-04-01-gap-2
#548Peripheral-to-Central Inflammation Circuit BreakerIL1B0.626$0.67SDA-2026-04-16-gap-b
#549Enteric Nervous System Prion-Like Propagation BlockadeTLR4, SNCA0.625$0.67SDA-2026-04-01-gap-2
#550APOE4-Targeted Ultrasonic Lipidation Enhancement for Gamma Oscillation Restoration in Alzheimer's DiseaseAPOE/PVALB0.625$0.61-
#551H7: Aberrant RNA Template Switching Converts Granules to Aggregation ProneG3BP1, DDX3X, DDX60.625$0.62SDA-2026-04-06-gap-p
#552PINK1/Parkin-Independent Mitophagy Bypass for Enhanced Donor MitochondriaBNIP3/BNIP3L0.624$0.66sda-2026-04-01-gap-2
#553Conditional CRISPR Kill Switches for Aberrant Protein ClearanceUBE3A, PARK2, PINK10.624$0.66SDA-2026-04-03-gap-c
#554Serine/Arginine-Rich Protein Kinase ModulationSRPK10.624$0.67sda-2026-04-01-gap-0
#555Microglial TREM2-Independent Pathway ActivationDAP12, SYK, PLCG20.623$0.66SDA-2026-04-03-gap-d
#556Myelin Sulfatide RestorationGAL3ST10.623$0.66SDA-2026-04-03-gap-a
#557TFEB-PGC1α Mitochondrial-Lysosomal DecouplingTFEB0.622$0.66SDA-2026-04-03-gap-a
#558Cholesterol-CRISPR Convergence Therapy for NeurodegenerationHMGCR, LDLR, APOE regulatory regions0.622$0.65SDA-2026-04-03-gap-c
#559TOM/TIM Complex Disruption Triggering Mitochondrial Integrated Stress Response (mtISR)TOMM40, TOMM70, CLPP0.622$0.62SDA-2026-04-08-gap-p
#560Pharmacological Enhancement of APOE4 GlycosylationST6GAL1, FUT80.622$0.66sda-2026-04-01-gap-0
#561Dual-Phase Medium-Chain Triglyceride InterventionHMGCS2/CPT1A0.622$0.61SDA-2026-04-04-gap-d
#562Microglial ACE Enhancement for Amyloid ClearanceACE0.622$0.65SDA-2026-04-03-gap-a
#563SYNJ1 Aggregation and Solubility Loss Impairs PI(4,5)P2 Cycling at Synaptic TerminalsSYNJ1, INPP5A, PIK3CA, PLCG10.621$0.66SDA-2026-04-16-gap-d
#564Designer TRAK1-KIF5 fusion proteins accelerate therapeutic mitochondrial deliveryTRAK1_KIF5A0.621$0.66sda-2026-04-01-gap-v
#565TREM2 Agonism to Reprogram Infiltrated Monocytes Toward Neuroprotective PhenotypeTREM20.620$0.61SDA-2026-04-13-gap-d
#566CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 DeliveryHDAC3 (class I histone deacetylase)0.620$0.62SDA-2026-04-08-gap-d
#567Cross-Cell Type Synaptic Rescue via Tripartite Synapse RestorationSYN1, SLC1A2, and CX3CR10.620$0.65SDA-2026-04-03-gap-s
#568SUV39H1 Restoration Represses Aberrant Transposon Expression in Aging NeuronsSUV39H1 (KMT1A)0.620$0.62SDA-2026-04-10-gap-2
#569TET Enzyme-Mediated 5hmC Restoration as Neuronal Rejuvenation StrategyTET2; TET30.620$0.62SDA-2026-04-10-gap-2
#570Synaptic RNA Metabolism DysregulationTARDBP0.620$0.62SDA-2026-04-08-gap-p
#571H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier RestorationIL-22, REG3G, zonulin0.620$0.65SDA-2026-04-15-gap-p
#572Chaperone-Degradation Coupling Prevents Aggregate Persistence by Shunting Seeds to the ProteasomeSTUB1 (CHIP), UPS pathway0.620$0.62SDA-2026-04-06-gap-d
#573Enhanced MCU Activity Primes mPTP Opening in Motor NeuronsMCU complex (MICU1/MICU2), mitochondrial calcium regulatory proteins0.620$0.62SDA-2026-04-07-gap-p
#574Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic ShiftHIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)0.620$0.62SDA-2026-04-06-gap-p
#575Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTDTARDBP, splicing targets (Sortilin1, Synaptojanin1)0.620$0.62SDA-2026-04-02-gap-2
#576Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 inflammasome activation without impairing normal proteolysisCTSB0.620$0.62SDA-2026-04-04-gap-l
#577C1Q-Induced Foam Cell Formation via Scavenger Receptor UpregulationC1QA/C1QC0.620$0.62SDA-2026-04-07-gap-p
#578Subtle NMDAR Inhibition Attenuates Excitotoxicity-Driven Tau Release from Hypersynchronized CircuitsGRIN2B0.620$0.62SDA-2026-04-04-gap-2
#579Tau fibrils expose neuronal phosphatidylserine and heat-shock protein 70, driving microglial non-complement synaptic engulfment in primary tauopathiesPhosphatidylserine, TIMD4, HSPA1A/HSPA1B, SCARF1, LRP80.620$0.62SDA-2026-04-02-gap-s
#580BMP4 Pathway Inhibition for Oligodendrocyte Myelination SupportBMP4 and BMPR1A0.620$0.66SDA-2026-04-03-gap-s
#581Microglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutamate ToxicitySLC7A110.620$0.60SDA-2026-04-16-gap-f
#582J-protein co-chaperone repertoire enables selective recognition of pathogenic conformersDNAJB6, DNAJB2, HSPA8, HSPA1A0.620$0.62SDA-2026-04-10-gap-d
#583Microglial Metabolic Trained Immunity via mTOR-HIF1α AxisMTOR/HIF1α0.620$0.62SDA-2026-04-07-gap-d
#584CSF Biomarker-Guided ABCA7 Therapeutic DosingABCA7 with biomarker-guided dosing0.619$0.61SDA-2026-04-14-gap-p
#585Lysosomal pH Restoration Upstream of TFEBATP6V1A0.619$0.65SDA-2026-04-03-gap-d
#586PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-Induced SPP1 UpregulationSPP10.618$0.62SDA-2026-04-06-gap-p
#587BH4 Cofactor Restoration as Primary Driver of >500-Fold Dopamine ElevationGCH1, TH, BH4 pathway0.618$0.61SDA-2026-04-13-gap-p
#588Neuronal Integrated Stress Response ModulationEIF2AK3 (PERK) and EIF2B complex0.618$0.65SDA-2026-04-03-gap-s
#589Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1C3/C3aR0.618$0.62SDA-2026-04-07-gap-p
#590Low Complexity Domain Cross-Linking InhibitionTGM20.617$0.66sda-2026-04-01-gap-0
#591LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP1 InductionSPP10.617$0.62SDA-2026-04-06-gap-p
#592Perinatal Immune Challenge PreventionMultiple0.616$0.65SDA-2026-04-04-gap-2
#593NAMPT-Centered NAD+ Restoration to Reverse Basal Forebrain Cholinergic Neuron Metabolic FailureNAMPT,SIRT1,PGC1A0.616$0.65SDA-2026-04-16-gap-p
#594Spatially-Targeted Regional Vulnerability PreventionRegional vulnerability genes0.616$0.65SDA-2026-04-03-gap-s
#595Mitochondrial-Cytokine Axis ModulationMitochondrial respiratory complexes and inflammatory cytokine receptors0.616$0.65SDA-2026-04-03-gap-a
#596MFN2-PACS2 Axis at MAMs Coordinates Mitophagy-ER-Phagy SyncMFN2 (MFN2), PACS2 (PACS2)0.615$0.61SDA-2026-04-07-gap-p
#597Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic WindowsTFEB, MAPK14, MAPKAPK2, IL6, CXCL10.614$0.61SDA-2026-04-07-gap-d
#598Dose-Response Framework: PINK1/Parkin Mitophagy as the Critical Mediator Linking HBOT Parameters to Tau Clearance-0.614$0.60SDA-2026-04-16-gap-p
#599Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory CascadeAGER0.613$0.65SDA-2026-04-01-gap-2
#600FUS Mutations Alter Stress Granule Material Properties to Confer Autophagy ResistanceFUS0.613$0.61SDA-2026-04-06-gap-p
#601Trinucleotide Repeat Sequestration via CRISPR-Guided RNA TargetingHTT, DMPK, repeat-containing transcripts0.613$0.64SDA-2026-04-03-gap-c
#602Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic EngineeringTDC0.612$0.64SDA-2026-04-01-gap-2
#603Optogenetic Control of Mitochondrial Transfer NetworksChR20.612$0.65sda-2026-04-01-gap-2
#604Complement-Mediated Synaptic Pruning DysregulationC1QA0.612$0.65SDA-2026-04-03-gap-a
#605Test: TREM2 enhances amyloid clearance-0.612$0.61-
#606Synaptic Pruning Precision TherapyC1QA, C3, CX3CR1, CX3CL10.612$0.65SDA-2026-04-04-gap-2
#607CaMKII-Dependent Synaptic Circuit AmplificationCAMK2A0.611$0.65SDA-2026-04-03-26abc
#608HDAC3-Dependent A1 Astrocyte Commitment WindowHDAC30.611$0.61SDA-2026-04-07-gap-d
#609Pharmacogenomic CNS Drug Optimization PlatformCYP450 enzymes, transporters, and drug targets0.611$0.60SDA-2026-04-04-gap-d
#610Epigenetic Memory Reprogramming for Alzheimer's DiseaseBDNF, CREB1, synaptic plasticity genes0.611$0.64SDA-2026-04-03-gap-c
#611APOE4-Lipid Metabolism CorrectionAPOE0.610$0.64SDA-2026-04-04-gap-2
#612Female microglia exhibit heightened complement gene expression and pruning capacity via estrogen-regulated epigenetic sensitization, explaining the female AD risk advantageESR2 (NR3A2), KDM6A (UTX), C1QA, C1QB, NFKB10.610$0.61SDA-2026-04-02-gap-s
#613Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB SignalingCREB1, BDNF, NTRK2 (TrkB)0.610$0.61SDA-2026-04-07-gap-p
#614Astrocyte LRP1-mediated tau uptake and APOE4-dependent secretion creates regional susceptibility gradientsLRP10.610$0.61SDA-2026-04-07-gap-d
#615H2: H3K9me3 Heterochromatin Collapse Enables Cryptic Transcription of Repetitive ElementsSUV39H1, CBX5 (HP1α), H3K9me3 mark0.610$0.61SDA-2026-04-04-gap-2
#616GDNF Gradient Establishment by Schwann Cells Enables Motor Re-innervationGDNF0.610$0.64SDA-2026-04-14-gap-p
#617Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease PathologymiR-1550.610$0.61SDA-2026-04-06-gap-p
#618Tau Cross-Seeding and InteractionMAPT0.610$0.61SDA-2026-04-08-gap-p
#619APOE4 preferentially signals through LRP1 over LDLR, altering endosomal cholesterol trafficking and causing lysosomal cholesterol sequestration that drives lysosomal dysfunction and inflammationLRP1, NPC1, CTSD0.610$0.61SDA-2026-04-04-gap-a
#620H2: Perforant Path Synapse Loss via Early Complement Cascade ActivationC1QA, C1QB, C3, ITGAM0.610$0.61SDA-2026-04-02-gap-e
#621H1: Senolytic Clearance of Senescent APOE4 AstrocytesCDKN2A (p16Ink4a)0.610$0.61SDA-2026-04-06-gap-d
#622ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberrant Condensate StabilizationG3BP10.610$0.61SDA-2026-04-06-gap-p
#623Blocking Tau Packaging into Small Extracellular Vesicles via ESCRT-III PathwayPDGRIP1L (ALIX)0.610$0.61SDA-2026-04-04-gap-t
#624Ketone-Based Metabolic Switching to Restore PV Interneuron FunctionSIRT3, PVALB0.609$0.60SDA-2026-04-16-gap-2
#625Microglial priming is primarily epigenetic, with metabolic changes acting as coupled consequences or cofactorsKDM6B0.609$0.61SDA-2026-04-07-gap-d
#626HIF1A stabilization lowers the activation threshold of circadian-disrupted microgliaHIF1A0.609$0.61SDA-2026-04-07-gap-d
#627Temporal TFEB Modulation TherapyTFEB0.609$0.65SDA-2026-04-03-gap-d
#628The Glial Ketone Metabolic Shunt HypothesisHMGCS20.608$0.64SDA-2026-04-02-gap-v
#629Calmodulin isoform switching from CaMK to calcineurin activation upon lysosomal permeabilizationCALM1/CALM2/CALM30.607$0.61SDA-2026-04-07-gap-p
#630Correcting Gut Microbial Dopamine Imbalance to Support Systemic Dopaminergic FunctionDDC0.606$0.65SDA-2026-04-01-gap-2
#631Circadian-Gated Ketone Window HypothesisOXCT10.606$0.66SDA-2026-04-03-gap-d
#632P2RY12-mediated autophagy inhibition in cerebral VSMCs impairs CAA clearanceP2RY120.605$0.60SDA-2026-04-07-gap-p
#633Microbiome-Derived Tryptophan Metabolite NeuroprotectionAHR, IL10, TGFB10.605$0.65SDA-2026-04-01-gap-2
#634DAPK1 Inhibition as Dual-Mechanism Neuroprotection Against Tau-Induced DestabilizationDAPK10.604$0.63SDA-2026-04-15-gap-p
#635TREM2-Microglial Clearance Enhancement as Common Mechanism for Injury PreventionTREM20.604$0.59SDA-2026-04-14-gap-p
#636NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for Reverse Senescence-0.602$0.60SDA-2026-04-16-gap-p
#637Selective TFEB Cofactor EnhancementTFE30.602$0.64SDA-2026-04-03-gap-d
#638STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Interruption of IFN-I Feedback LoopingTMEM173 (STING)0.601$0.60SDA-2026-04-15-gap-p
#639TREM2-Dependent Senescent Microglia Disrupt Astrocyte Communication NetworksTREM2/TYROBP0.600$0.54SDA-2026-04-03-gap-a
#640C1Q-Mediated Defective Efferocytosis Driving Necrotic Core ExpansionC1QA/C1QC0.600$0.60SDA-2026-04-07-gap-p
#641TREM2-Mediated Oligodendrocyte-Microglia Cross-talk in White Matter NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#642TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement CascadeTNF; TNFRSF1A; C1R; C1S0.600$0.60SDA-2026-04-08-gap-p
#643mTORC1 Hyperactivation Impairs Autophagic Flux and Drives SenescenceMTOR/TFEB/TFE30.600$0.60SDA-2026-04-06-gap-p
#644Aberrant Galectin-3 Expression on Stressed Synapses Creates Bridging MoleculesLGALS3 (Galectin-3)0.600$0.60SDA-2026-04-07-gap-p
#645Displacement of G3BP1 RGG Box from Target RNA via Ubiquitin-Mediated AllosteryG3BP10.600$0.60SDA-2026-04-07-gap-p
#646Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-17, blocking autophagosome-lysosome fusionTARDBP0.600$0.60SDA-2026-04-08-gap-p
#647TREM2-Mediated Astroglial Reactivity in NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#648APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex NeurodegenerationAPOE40.600$0.60SDA-2026-04-06-gap-p
#649H4: Hyperconnected Hub Status Creates Proteostatic Traffic JamsERN1 (IRE1α), TFG, ATG9A0.600$0.60SDA-2026-04-02-gap-e
#650Selective C1q-CRP vs. C1q-IgG Axis InhibitionC1QA/C1QB/C1QC, CRP, FCGR1A0.599$0.61SDA-2026-04-16-gap-p
#651Oligodendrocyte-Targeted Myelin Sulfatide Restoration TherapyCST, GAL3ST10.599$0.63SDA-2026-04-03-gap-d
#652Differential Interneuron Optogenetic Restoration TherapyPVALB/SST0.599$0.63SDA-2026-04-03-26abc
#653OPC differentiation blockade contributes to white matter degeneration in early-stage ADPDGFRA0.599$0.65SDA-2026-04-04-analy
#654Metabolic Reprogramming via Coordinated Multi-Gene CRISPR CircuitsPGC1A, SIRT1, FOXO3, mitochondrial biogenesis genes0.599$0.63SDA-2026-04-03-gap-c
#655Brain Insulin Resistance with Glucose Transporter DysfunctionGLUT3/GLUT40.596$0.63SDA-2026-04-02-gap-v
#656Programmable Neuronal Circuit Repair via Epigenetic CRISPRNURR1, PITX3, neuronal identity transcription factors0.596$0.63SDA-2026-04-03-gap-c
#657Multi-Modal CRISPR Platform for Simultaneous Editing and MonitoringDisease-causing mutations with integrated reporters0.596$0.63SDA-2026-04-03-gap-c
#658Aβ42 oligomers drive TDP-43 phosphorylation at s409/410 through CDK5/p25 activation specifically in AD, generating a phospho-signature distinct from ALS/FTLDCDK5R1 (p25 regulatory subunit)0.595$0.59SDA-2026-04-07-gap-p
#659Aβ-induced downregulation of circPDS5B derepresses TDP-43 mRNA translation in limbic neurons, causing proteostatic overload and aggregation specifically in ADcircPDS5B (hsa_circ_0083342) / TARDBP0.595$0.59SDA-2026-04-07-gap-p
#660Netrin-1 Gradient RestorationNTN10.595$0.66sda-2026-04-01-gap-0
#661TREM2-mediated microglial tau clearance enhancementTREM20.594$0.84SDA-2026-04-04-gap-t
#662NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement AmplificationNAMPT, SIRT10.592$0.59SDA-2026-04-16-gap-2
#663TREM2 Signaling Bifurcation with Independent TYROBP-Independent Homeostatic MaintenanceTREM20.591$0.60SDA-2026-04-14-gap-p
#664Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A2 PolarizationAHR, CYP1A1, NFKB1, IL60.591$0.60SDA-2026-04-14-gap-p
#665TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse LossTREM2,C1Q0.591$0.63SDA-2026-04-16-gap-p
#666Bacterial Enzyme-Mediated Dopamine Precursor SynthesisTH, AADC0.590$0.66SDA-2026-04-01-gap-2
#667G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG-Targeting InterventionsG3BP10.590$0.59SDA-2026-04-06-gap-p
#668Neuronal MHC Class I Expression as a Selectivity DeterminantH2-Kb (H2-K1), Lilrb4 (LilrB2)0.590$0.59SDA-2026-04-07-gap-p
#669Competition with G3BP1-Caprin1/FMRP Scaffold FormationG3BP10.590$0.59SDA-2026-04-07-gap-p
#670M1 Muscarinic Receptor Agonism as Pharmacological Exercise SubstituteCHRM10.589$0.58SDA-2026-04-14-gap-p
#671AP1S1-Mediated Vesicular Transport RestorationAP1S10.588$0.62SDA-2026-04-03-gap-a
#672Cardiovascular-Neuroinflammation Crosstalk InterruptionIL1B, TNFA, NLRP30.587$0.62SDA-2026-04-04-gap-2
#673TREM2-Mediated Oligodendrocyte-Microglia Signaling in White Matter NeurodegenerationTREM20.587$0.53SDA-2026-04-03-gap-a
#674Microglia-Derived Extracellular Vesicle Engineering for Targeted Mitochondrial DeliveryRAB27A/LAMP2B0.587$0.63sda-2026-04-01-gap-2
#675TNFRSF25-Mediated Aging Exosome Pathway InhibitionTNFRSF250.587$0.62SDA-2026-04-03-gap-a
#676REDD1-mTOR Axis as the Master Regulator — Preservation Over ChelationDDIT4 (REDD1), MTOR0.586$0.58SDA-2026-04-15-gap-p
#677Senescence-Tau Decoupling TherapyCDKN2A0.585$0.62SDA-2026-04-03-gap-a
#678Mitochondrial-Lysosomal Coupling EnhancerLAMTOR10.585$0.62SDA-2026-04-03-gap-d
#679Gut-Brain Axis Microbiome ModulationGPR43, GPR109A0.585$0.62SDA-2026-04-04-gap-2
#680P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and neurovascular unit dysfunctionP2RY120.585$0.58SDA-2026-04-07-gap-p
#681ALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding InterfacesG3BP1, G3BP20.585$0.58SDA-2026-04-06-gap-p
#682PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineurin→TFEB Cascade in ALS Motor NeuronsPIKFYVE/MCOLN1/PPP3CB/TFEB0.584$0.62SDA-2026-04-13-gap-p
#683NOMO1-Mediated Neuronal Resilience EnhancementNOMO10.584$0.63SDA-2026-04-03-gap-a
#684APOE4 Creates Accelerated, Compressed Reversibility WindowAPOE/TREM2 axis, APOE-TREM2 physical interaction0.584$0.58SDA-2026-04-06-gap-d
#685IGFBPL1-Mediated Homeostatic RestorationIGFBPL10.584$0.62SDA-2026-04-04-gap-2
#686FcRn Transport Bypass StrategyLDLR0.583$0.62SDA-2026-04-12-gap-d
#687Gamma Entrainment Synergy: HBOT-Enhanced Cerebral Perfusion Amplifies SST Interneuron-Targeted Neuromodulation-0.583$0.57SDA-2026-04-16-gap-p
#688GPC4/HSPGs Collaborate with ApoE Isoforms to Dictate Tau Conformational Strain Uptake EfficiencyGPC4/APOE0.583$0.58SDA-2026-04-15-gap-d
#689Pharmacological P2RY12 inhibition (ticagrelor/clopidogrel) as repurposing probe for neurovascular outcomesP2RY120.583$0.58SDA-2026-04-07-gap-p
#690ITGAM/CD11b direct binding explains microglial phagocytosis blockadeITGAM0.582$0.58SDA-2026-04-21-gap-d
#691TREM2 Promoter Silencing via DNA HypermethylationTREM20.580$0.58SDA-2026-04-07-gap-d
#692AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic NeurodegenerationAQP4; STAT3; MMP90.580$0.58SDA-2026-04-07-gap-p
#693ALOX15 Inhibition Combined with Selenium Augmentation for Synergistic Ferroptosis BlockadeALOX15, SELENOP0.580$0.57SDA-2026-04-16-gap-f
#694H7: Dual-Target Strategy (Senolytics + APOE4→3 Conversion)APOE; CDKN2A0.580$0.58SDA-2026-04-06-gap-d
#695Nuclear Export Deficits Increase Cytosolic TDP-43 BurdenXPO1/CRM1, ALYREF, THOC1/THOC2, TDP-43 NLS0.580$0.58SDA-2026-04-07-gap-p
#696CHIP-mediated ubiquitination selectively targets oligomeric pathologic conformers for proteasomal degradationSTUB1 (CHIP), HSPA8, VCP, PSMD40.580$0.58SDA-2026-04-10-gap-d
#697APOE4 Structural Correction by Small Molecule CorrectorsAPOE40.580$0.58SDA-2026-04-02-gap-a
#698Limited Calcium Release Without Sufficient Cathepsin EffluxTRPML1/MCOLN1, Calcineurin/NFAT0.580$0.58SDA-2026-04-07-gap-p
#699H5: Complement Dysregulation Drives Synapse Loss via Senescent APOE4 AstrocytesC3; C3AR1; C5AR10.580$0.58SDA-2026-04-06-gap-d
#700Microglial Replacement and Ontogeny ShiftCCR20.580$0.58SDA-2026-04-07-gap-d
#701Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement BiosynthesisNFKB1; IKBKB; C1QA; C30.580$0.58SDA-2026-04-08-gap-p
#702Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 SignalingNLRP3, LRP1, IL1B, TNF0.580$0.58SDA-2026-04-07-gap-p
#703TREM2-Driven Phagocytic Receptor Cascades Determine Mitochondrial Antigen Presentation vs. Intracellular MitophagyTREM20.580$0.58SDA-2026-04-08-gap-p
#704Dysregulated G3BP1 Signaling Impairs Local Translation in Neuronal Processes, Contributing to Synaptic DysfunctionG3BP10.580$0.58SDA-2026-04-06-gap-p
#705LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and downstream NLRP3 activationLAMP2 (LGMN)0.580$0.58SDA-2026-04-04-gap-l
#706APOE4 drives astrocyte metabolic reprogramming toward glycolysis via PGC-1α suppression, reducing fatty acid oxidation and promoting lipogenesis that feeds pathological lipid droplet formationPPARGC1A (PGC-1α), SIRT1, SREBF1 (SREBP1c)0.580$0.58SDA-2026-04-04-gap-a
#707Astrocyte cGAS/STING Activation Converts Protective into Destructive NeuroinflammationSTING (TMEM173) in astrocytes (GFAP+ cells)0.580$0.58SDA-2026-04-07-gap-p
#708Oxygen Pressure-Dependent BDNF Cascade: DHHC2/PSD95 Stabilization for Synaptic Rescue-0.580$0.57SDA-2026-04-16-gap-p
#709Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Through Attenuated ChemotaxisP2RY120.580$0.58SDA-2026-04-06-gap-p
#710Structure-interacting small molecules that stabilize the APOE4 molten globule domain (Domain III) can restore near-wildtype lipid-binding capacity, reducing lipid droplet pathologyAPOE (protein structure stabilizer)0.580$0.58SDA-2026-04-04-gap-a
#711αvβ3 Integrin-FAK-SYK-CARD9/NF-κB PathwayITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD90.580$0.58SDA-2026-04-06-gap-p
#712Disrupted AQP4-Mediated K+ Spatial Buffering Causes Neuronal Hyperexcitability and Seizure SusceptibilityAQP4; KCNJ10 (Kir4.1); ATP1A20.580$0.58SDA-2026-04-07-gap-p
#713Complement-Mediated Synaptic ProtectionC1QA0.580$0.62SDA-2026-04-04-gap-2
#714IGFBPL1-Mediated Microglial ReprogrammingIGFBPL10.579$0.62SDA-2026-04-04-gap-2
#715TREM2-Astrocyte Communication in Microglial DysfunctionTREM20.579$0.00SDA-2026-04-03-gap-a
#716Spatial Transcriptome-Guided Precision Cell TherapySOX10 and DLX1/20.578$0.62SDA-2026-04-03-gap-s
#717NAD+/SARM1 Axis Provides Metabolic Feedback Coupling Mitophagy to ER-PhagySARM1 (SARM1), PARP1, SIRT1, SIRT30.578$0.58SDA-2026-04-07-gap-p
#718Hepcidin-Iron Set Point Hypothesis-0.577$0.57SDA-2026-04-13-gap-p
#719H4: Age-Related Hsp70 Chaperone Decline Blocks Granule ReversibilityHSPA1A/HSPA1B, DNAJB6, DNAJB80.577$0.58SDA-2026-04-06-gap-p
#720TDP-43 Cryptic Exon–Targeted ASOs to Restore Hippocampal Gamma OscillationsTARDBP (TDP-43) / cryptic splice sites in GABAergic transcripts (DLGAP1, KCNQ2, GABRA1)0.577$0.57SDA-2026-04-13-gap-2
#721Dynamic Microglial Phenotype Switching Biomarker Panel for Neuroinflammatory Treatment StratificationTREM20.577$0.58SDA-2026-04-16-gap-p
#722TBK1 Phosphorylation State Creates Phospho-Regulated Peripheral Retention ThresholdTBK10.577$0.58SDA-2026-04-08-gap-p
#723LRP1-Dependent Tau Uptake DisruptionLRP10.576$0.79SDA-2026-04-04-gap-t
#724Oligodendrocyte Progenitor Cell Metabolic ReprogrammingPDK1, PFKFB3, LDHA0.575$0.61SDA-2026-04-03-gap-d
#725Sequential TRPML1 Activation Following Autophagy PrimingMCOLN1 (TRPML1), ATG70.575$0.56SDA-2026-04-16-gap-d
#726TREM2-Senescence Cascade in Astrocyte-Microglia Communication BreakdownTREM20.574$0.00SDA-2026-04-03-gap-a
#727TREM2-P2RY12 Balance Restoration TherapyTREM20.571$0.61SDA-2026-04-04-gap-2
#728Disease-Associated Microglia (DAM) Program Drives IBA1 DownregulationTREM2/TYROBP0.571$0.57SDA-2026-04-07-gap-p
#729PINK1/PARK2-Mediated Mitophagy Enhancement for Neuroinflammation ControlPINK10.571$0.57SDA-2026-04-03-gap-i
#730VPS34 Complex I Subunit Heterogeneity Dictates Organelle-Specific vs. Bulk AutophagyPIK3C3/VPS34, ATG14L, UVRAG, NRBF20.571$0.57SDA-2026-04-07-gap-p
#731Neuronal Subtype-Specific Alpha-Synuclein Expression NormalizationSNCA0.571$0.60SDA-2026-04-03-gap-d
#732VCP-Mediated Autophagy EnhancementVCP0.571$0.76SDA-2026-04-04-gap-t
#733Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 InhibitionHDAC6 (class IIb histone deacetylase)0.570$0.57SDA-2026-04-08-gap-d
#734Blocking Astrocyte-Mediated Tau Re-Spreading via Cx43 Hemichannel InhibitionGJA1 (Connexin-43)0.570$0.57SDA-2026-04-04-gap-t
#735LRP1-mediated synaptic uptake drives early entorhinal-hippocampal tau propagation (Braak I-II)LRP10.570$0.57SDA-2026-04-07-gap-d
#736Hsp70-based therapy to prevent lysosomal membrane permeabilization and cathepsin release in ADHSPA1A0.570$0.57SDA-2026-04-04-gap-l
#737CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estrogen Receptor-alpha Suppression of NLRP3ESR10.570$0.57SDA-2026-04-06-gap-p
#738Blocking Exosomal Tau Uptake at Neuronal LRP1 Receptors Disrupts Interneuronal PropagationLRP10.570$0.57SDA-2026-04-04-gap-2
#739Direct NF-κB Transcriptional Regulation of C1q Genes in MicrogliaRELA; C1QA/C1QB/C1QC0.570$0.57SDA-2026-04-08-gap-p
#740Tau-Independent Microtubule Stabilization via MAP6 EnhancementMAP60.567$0.73sda-2026-04-01-gap-0
#741ER Stress Reduction as Adjunctive Therapy to Support AutophagyHFE (H63D variant)0.566$0.56SDA-2026-04-15-gap-p
#742Synergistic enhancement of autophagy and lysosomal biogenesis by combined mTOR inhibition and TFEB activationMTOR, TPCN2, TFEB0.565$0.57SDA-2026-04-04-gap-l
#743Temporal Gating of Microglial ResponsesCLOCK, ARNTL0.565$0.63SDA-2026-04-04-gap-2
#744Closed-loop tACS targeting EC-II somatostatin interneurons to restore dendritic integration and prevent tau-mediated HCN channel dysfunction in ADSST0.564$0.56SDA-2026-04-03-26abc
#745Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymphatic-mediated amyloid clearance and secondary PV interneuron disinhibition in Alzheimer's diseaseAQP40.564$0.56SDA-2026-04-03-26abc
#746Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via indirect somatostatin interneuron disinhibition in Alzheimer's diseaseSST0.564$0.56SDA-2026-04-03-26abc
#747Closed-loop transcranial focused ultrasound with real-time gamma feedback to restore PV interneuron function in Alzheimer's diseasePVALB0.564$0.56SDA-2026-04-03-26abc
#748Closed-loop transcranial focused ultrasound targeting entorhinal PV interneurons to restore AnkyrinG-dependent AIS integrity and hippocampal gamma synchrony in Alzheimer's diseasePVALB0.564$0.56SDA-2026-04-03-26abc
#749Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Prevent SASP-Driven Complement Cascade AmplificationCDKN2A (p16^Ink4a), CDKN1A (p21^Cip1/Waf1)0.564$0.56SDA-2026-04-15-gap-p
#750Fractalkine Axis Amplification via CX3CR1 Positive Allosteric ModulatorsCX3CR10.563$0.69sda-2026-04-01-gap-v
#751C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by PIKFYVE Inhibition via Lysosomal Exocytosis RestorationC9orf72/SMCR8/RAB7A/PIKFYVE0.562$0.60SDA-2026-04-13-gap-p
#752HCN1-Mediated Resonance Frequency Stabilization TherapyHCN10.562$0.73sda-2026-04-01-gap-0
#753H3: Reelin Signaling Deficiency Uncouples Layer II Neurons from Grid Cell CouplingRELN, LRP8, GSK3B0.560$0.56SDA-2026-04-02-gap-e
#754P2X7R PET Imaging for NLRP3 Inflammasome-Associated PrimingP2RX7/NLRP30.560$0.56SDA-2026-04-06-gap-d
#755AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metabolic Coupling DisruptionAQP4; SLC16A1 (MCT1); SLC16A3 (MCT4)0.560$0.56SDA-2026-04-07-gap-p
#756Persistent γH2AX+53BP1 Foci with DREAM Complex Activation Defines Irreversibly Arrested MicrogliaH2AFX (γH2AX), TP53BP1, DREAM complex (LIN9, LIN37, RBL2, E2F4)0.560$0.56SDA-2026-04-06-gap-d
#757Complement C1q Suppression as Mechanism Linking Exercise Plasma to PV Interneuron ProtectionC1QA0.560$0.55SDA-2026-04-14-gap-p
#758GCH1/BH4 Axis Stabilization for Dual Ferroptosis and Mitochondrial ProtectionGCH1, BH40.560$0.55SDA-2026-04-16-gap-f
#759TFEB Activation Clears Tau-Loaded Endolysosomal Compartments, Preventing Release for Transcellular SpreadingTFEB0.560$0.56SDA-2026-04-04-gap-2
#760MOG-IgG induces spinal cord demyelination through Fcγ receptor-dependent macrophage activationMOG, FCGR1A, FCGR3A, FCGR2A, SYK, IRAK40.560$0.56SDA-2026-04-08-gap-p
#761Post-Translational Modification Codes Determine Interaction SpecificityG3BP1, PRMT1, PRMT5, ATM, ATR0.560$0.56SDA-2026-04-07-gap-p
#762Temporal cGAS-STING Activation Stage-Specific Therapeutic TargetingSTING (TMEM173)0.560$0.56SDA-2026-04-07-gap-p
#763TRPML1-PINK1/Parkin Axis Coordinates Mitophagy with Lysosomal BiogenesisMCOLN1, PINK1, PARK2, TFEB, LRRK20.560$0.55SDA-2026-04-16-gap-d
#764Multi-Chaperone System Co-Activation Prevents Saturation Through Complementary Substrate RecognitionDNAJB1, HSP90AA1/HSP90AB1, STIP1 (HOP)0.560$0.56SDA-2026-04-06-gap-d
#765AMPK Activation to Restore Autophagy and Clear α-Synuclein Aggregates-0.559$0.56SDA-2026-04-17-gap-p
#766Real-time closed-loop transcranial focused ultrasound targeting PVALB interneurons with continuous gamma oscillation feedback monitoring for precision neuromodulation in Alzheimer's diseasePVALB0.559$0.56SDA-2026-04-03-26abc
#767Extracellular Vesicle Biogenesis ModulationCHMP4B0.558$0.68SDA-2026-04-04-gap-t
#768Circadian-Gated Maresin Biosynthesis AmplificationALOX120.557$0.74sda-2026-04-01-gap-0
#769Test: TREM2 enhances amyloid clearance-0.555$0.55-
#770Optogenetic restoration of hippocampal gamma oscillations via channelrhodopsin-2 expression in PV interneurons for Alzheimer's disease treatmentPVALB0.555$0.00SDA-2026-04-03-26abc
#771GluN2B-Mediated Microglial Activation and Tau PropagationGRIN2B0.555$0.56SDA-2026-04-03-26abc
#772Neuroplasticity-Enhanced Learning HypothesisBDNF0.555$0.59SDA-2026-04-04-gap-d
#773Ketone-Primed Thalamocortical Enhancement of Glymphatic Tau ClearanceGRIN2B0.555$0.56SDA-2026-04-03-26abc
#774Inhibitory Neuron-Selective WNT Signaling RestorationWNT3A, CTNNB1, TCF7L20.554$0.62SDA-2026-04-03-gap-d
#775Synaptic Vesicle Tau Capture InhibitionSNAP250.554$0.69SDA-2026-04-04-gap-t
#776Profilin-1 Cytoskeletal Checkpoint EnhancementPFN10.554$0.60SDA-2026-04-03-gap-a
#777Dual NF-κB/MMP Inhibition StrategyNFKB10.554$0.57SDA-2026-04-16-gap-b
#778APOE4 Isoform Correction via Lipidation Enhancement as CTE Risk MitigationAPOE0.552$0.54SDA-2026-04-14-gap-p
#779MFSD2A-Targeted Lysophosphatidylcholine-SPM Conjugates as CNS-Penetrant Pro-Resolving ProdrugsMFSD2A (SLC59A1)0.552$0.54SDA-2026-04-12-gap-d
#780HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.551$0.80SDA-2026-04-04-gap-t
#781Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation WindowsNLRP30.551$0.55SDA-2026-04-15-gap-p
#782Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via astrocytic calcium signaling and potassium buffering in Alzheimer's diseaseAQP40.551$0.00SDA-2026-04-03-26abc
#783Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional ControlSPP10.551$0.55SDA-2026-04-15-gap-p
#784H63D HFE Genotype-Guided Iron Chelation Therapy for Subset-Selected ALS PatientsHFE (H63D variant)0.550$0.54SDA-2026-04-16-gap-f
#785Oligodendrocyte DNA Repair EnhancementPARP10.550$0.59SDA-2026-04-03-gap-s
#786C1q Binding to Specific Synaptic Proteomes via Neurexin/Neuroligin ComplexesNRXN1, NLGN1 (Neuroligin 1)0.550$0.55SDA-2026-04-07-gap-p
#787RNA Sequence Elements as Primary Specificity DeterminantsTIA1, HuR, FMRP, G3BP10.550$0.55SDA-2026-04-07-gap-p
#788Surface Exposure of SENP1-β1 Integrin Complex Enables Targeted Senolytic EliminationSENP1, ITGB1 (β1 integrin), ITGAM (CD11b)0.550$0.55SDA-2026-04-06-gap-d
#789Digital Twin-Guided Metabolic ReprogrammingPPARGC1A/PRKAA10.550$0.70sda-2026-04-01-gap-0
#790H7: NEAT1 Epigenetic Rewiring Under Proteotoxic StressNEAT1, METTL14, YTHDC1 (m6A reader)0.550$0.55SDA-2026-04-04-gap-2
#791oxLDL/LOX-1/ROS Signaling Induces P2RY12 via Nrf2 ActivationOLR1 (LOX-1), NFE2L2 (Nrf2)0.550$0.55SDA-2026-04-07-gap-p
#792GPP Repeat Peptide-Fc Fusion for Enhanced Brain PenetrationSLC15A2 (PepT2); FCGRT (FcRn)0.550$0.55SDA-2026-04-02-gap-b
#793Disrupting Muscarinic M1/M3 Receptor-Mediated Tau Internalization and Synaptic TargetingCHRM1 (M1R)0.550$0.55SDA-2026-04-04-gap-t
#794H2: SASP Neutralization via JAK/STAT Inhibition Preserves Astrocyte FunctionIL6R; JAK1; STAT30.550$0.55SDA-2026-04-06-gap-d
#795Combined NAMPT-Alectinib Targeting of SASP-Complement CascadeNAMPT, SIRT1, C1QA/C1QB/C1QC, IL1B0.549$0.55SDA-2026-04-16-gap-p
#796YWHAG-Mediated TFEB Subcellular TargetingYWHAG0.549$0.62SDA-2026-04-03-gap-d
#797Perinatal Hypoxia-Primed Microglia TargetingHIF1A, NFKB10.548$0.59SDA-2026-04-04-gap-2
#798TRIM21-Mediated Ubiquitination Creates Peripheral Epitope Gradient via K63-Linked Chain AccumulationTRIM210.548$0.55SDA-2026-04-08-gap-p
#799SYK-Independent TREM2 Pathways Remain Functional in TYROBP DeficiencySYK, TREM20.548$0.54SDA-2026-04-14-gap-p
#800Synaptic Vesicle Tau Capture InhibitionSNAP250.547$0.59SDA-2026-04-04-gap-t
#801Sensory-Motor Circuit Cross-Modal CompensationCHAT0.546$0.59SDA-2026-04-03-26abc
#802CD300f Immune Checkpoint ActivationCD300F0.545$0.61SDA-2026-04-03-gap-a
#803Trans-Synaptic Adhesion Molecule ModulationNLGN10.544$0.63SDA-2026-04-04-gap-t
#804Temporal Decoupling via Circadian Clock ResetCLOCK0.543$0.77sda-2026-04-01-gap-0
#805TREM2-GluN2B Circuit: Microglial Control of Thalamocortical Oscillations and Glymphatic Tau ClearanceTREM20.543$0.00SDA-2026-04-03-26abc
#806Epigenetic Reprogramming Required for Late-Stage Interventions (OSKM)DNA methylation machinery (DNMTs), H3K27ac modifiers (p300/CBP, HDACs)0.542$0.54SDA-2026-04-06-gap-d
#807Real-time closed-loop transcranial focused ultrasound targeting PV interneurons with API-integrated biomarker validation in Alzheimer's diseasePVALB0.542$0.00SDA-2026-04-03-26abc
#808Transient OCT4/SOX2/KLF4/c-MYC Expression Reverses Epigenetic Age and Restores Visual Function in Aged Retinal NeuronsOCT4/SOX2/KLF4/c-MYC (OSKM)0.540$0.54SDA-2026-04-04-gap-2
#809Synaptic Vulnerability Window Temporal Targeting: Transient SPP1 BlockadeSPP10.540$0.54SDA-2026-04-07-gap-p
#810N-acetylation Deficiency as Novel Metabolic Vulnerabilities in Sporadic ALSNAA10, NAA20, NAA800.540$0.54SDA-2026-04-02-gap-2
#811H5: Olfactory System as a Toxicant Funnel into Layer IINLRP3, CX3CR1, TLR40.540$0.54SDA-2026-04-02-gap-e
#812BAG3-Mediated Hsp70 Substrate RedistributionHSPA1A/Hsp70, BAG30.540$0.54SDA-2026-04-07-gap-p
#813Membrane interfacial selectivity for lipid-anchored pathologic conformersSNCA, HSPA8, DNAJB60.540$0.54SDA-2026-04-10-gap-d
#814circHomer1a Restoration as Neuroprotective Strategy in Synaptic DeclinecircHomer1a, miR-1961, HOMER10.540$0.54SDA-2026-04-02-gap-2
#815TAM Receptor (MERTK/AXL) Cross-RegulationMERTK, AXL, TYRO3, PROS1 (Protein S), GAS60.540$0.54SDA-2026-04-06-gap-p
#816Systemic IL-6–STAT3–Hepatic C3 Axis and BBB-Mediated Complement TranslocationIL6; STAT3; C30.540$0.54SDA-2026-04-08-gap-p
#817P2Y6R activation by UDP from damaged neurons drives microglial phagocytosis and exosomal re-secretion in mid-to-late diseaseP2RY60.540$0.54SDA-2026-04-07-gap-d
#818H6: Epigenetic Reset via APOE4→APOE3 Conversion Reverses SenescenceAPOE; HDAC1; EZH20.540$0.54SDA-2026-04-06-gap-d
#819Soluble CX3CL1 cleavage by ADAM proteases disengages fractalkine signaling, removing the neuronal 'don't eat me' signal from microglial CX3CR1CX3CL1, CX3CR1, ADAM10, ADAM170.540$0.54SDA-2026-04-02-gap-s
#820Transient Chaperone Priming Prior to Seed Inoculation Prevents Propagation by Reshaping Neuronal ProteostasisHSF1, NFE2L2 (NRF2), HSPA1A, DNAJB10.540$0.54SDA-2026-04-06-gap-d
#821Lysosomal Membrane Repair EnhancementCHMP2B0.538$0.72sda-2026-04-01-gap-0
#822Ferroptosis as Disease-Modifying Amplifier-0.538$0.54SDA-2026-04-18-gap-d
#823ABCA7-TREM2 Co-Targeting for Microglial Lipid HandlingABCA7 + TREM2 (combinatorial)0.538$0.54SDA-2026-04-14-gap-p
#824Glymphatic System-Enhanced Antibody Clearance ReversalAQP40.537$0.71sda-2026-04-01-gap-0
#825Test: TREM2 enhances amyloid clearance-0.537$0.54-
#826Cerebrospinal Fluid p-tau217-Guided Astrocyte-Derived Extracellular Vesicle Delivery of lncRNA-0021 in Early-Stage ADCSF p-tau217 (biomarker), lncRNA-0021, astrocyte-derived extracellular vesicles0.536$0.54SDA-2026-04-16-gap-p
#827Gamma-Entrained PV Interneuron Networks Enable Precision p-tau217-Guided lncRNA Exosome Therapy in ADPVALB, CREB1, lncRNA-0021/lncRNA-99690.536$0.54SDA-2026-04-16-gap-p
#828Gamma-Entrained PV Interneurons Enable p-tau217-Guided Precision Dosing of lncRNA Therapeutics in ADlncRNA-0021, PVALB, CREB10.536$0.54SDA-2026-04-16-gap-p
#829Cerebrospinal NFL-Triggered Liposome Dosing Maximizes lncRNA-0021 Therapeutic Window in ADCSF NFL (biomarker), lncRNA-0021, synthetic liposomes0.536$0.54SDA-2026-04-16-gap-p
#830CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering NF-κB-Dependent SPP1 TranscriptionSPP10.535$0.74SDA-2026-04-06-gap-p
#831NFκB/C1Q SASP Modulation for Synaptic Protection-0.534$0.53SDA-2026-04-16-gap-p
#832TREM2-Mediated Microglial Checkpoint TherapyTREM20.534$0.58SDA-2026-04-03-gap-s
#833Blood-Brain Barrier SPM Shuttle SystemTFRC0.533$0.76sda-2026-04-01-gap-0
#834Cryptic Exon Silencing RestorationTARDBP0.531$0.73sda-2026-04-01-gap-v
#835Oligodendrocyte Lineage Vulnerability: Early Myelination Disruption with Blocked DifferentiationPDGFRα0.530$0.53SDA-2026-04-02-gap-s
#836PI3P Generation at Damaged Lysosomes Promotes Membrane RepairPIK3C3/VPS34, CHMP2A0.530$0.53SDA-2026-04-07-gap-p
#837CX3CR1-Targeted AntimiR-155 Oligonucleotides for Microglial Priming ReversalMIR155 (microRNA-155)0.530$0.53SDA-2026-04-08-gap-d
#838Therapeutic Repurposing: C1-INH as Plaque-Stabilizing AgentC1R/C1S0.530$0.53SDA-2026-04-07-gap-p
#839NLRP3 Inflammasome Chromatin Priming Through H3K27ac AccumulationNLRP30.530$0.53SDA-2026-04-07-gap-d
#840C1Q-Angiogenic Axis Promoting Plaque NeovascularizationC1QA/C1QC0.530$0.53SDA-2026-04-07-gap-p
#841TSPO PET Kinetic Modeling for Priming State DiscriminationTSPO0.530$0.53SDA-2026-04-06-gap-d
#842H4: Polycomb Repression Relaxes at Neurodevelopment GenesEZH2, H3K27me3, CBX proteins0.530$0.53SDA-2026-04-04-gap-2
#843Modulating Tunneling Nanotube (TNT) Formation via M-Sec/Noradrenaline SignalingTNFRSF12A (M-Sec)0.530$0.53SDA-2026-04-04-gap-t
#844Astrocytic Lactate Shuttle Enhancement for Grid Cell BioenergeticsSLC16A20.529$0.69sda-2026-04-01-gap-0
#845DNMT1 Compensation Window During Synaptic Resilience PhaseDNMT10.528$0.53SDA-2026-04-07-gap-d
#846Cholinergic Attention Modulation HypothesisCHRNA70.528$0.57SDA-2026-04-04-gap-d
#847HCN1-Selective Blockade Normalizes Thalamic Rebound Bursting in P/Q Channel DeficiencyHCN10.526$0.54SDA-2026-04-14-gap-p
#848TREM2 Epigenetic Window for Microglial Lipid MetabolismTREM2/HDAC10.525$0.53SDA-2026-04-07-gap-d
#849TREM2-Dependent Microglial Control of Thalamocortical-Glymphatic Tau ClearanceTREM20.524$0.00SDA-2026-04-03-26abc
#850Circadian Clock Epigenetic Desynchronization WindowBMAL1/HDAC30.524$0.52SDA-2026-04-07-gap-d
#851Lamin B1 Degradation as Irreversibility GateLMNB1, LMNB2, NCOA4, SQSTM10.523$0.52SDA-2026-04-07-gap-d
#852Ancestry-Adapted Mitochondrial Rescue TherapyPPARGC1A, NRF1, TFAM0.523$0.52SDA-2026-04-04-gap-d
#853TREM2 Agonism to Redirect Microglia from Synaptic Pruning to OPTN-Deficient Neuron ProtectionTREM20.521$0.51SDA-2026-04-14-gap-p
#854Therapeutic Window Exists Through Activity-Dependent Regulation of Synaptic Vesicle PrimingVAMP2, VAMP3, Complexin-1/2, Munc13-10.520$0.52SDA-2026-04-06-gap-d
#855Dysregulated microglial glycolysis via HIF1α activation shifts the balance from neuroprotective surveillance to complement-mediated synapse engulfmentHIF1A, LDHA, LDHB, PKM2, TREM2, AMPK/mTOR0.520$0.52SDA-2026-04-02-gap-s
#856miR-143/145 Cluster Dysregulation Derepresses P2RY12 TranscriptionMIR143, MIR145, KLF40.520$0.52SDA-2026-04-07-gap-p
#857M-Sec/TNTA2-mediated tunneling nanotube formation drives glia-neuron tau propagation in mid-stagesTNFAIP20.520$0.52SDA-2026-04-07-gap-d
#858Restoring AQP4 Astrocyte Polarization Enhances Glymphatic Tau Clearance and Limits Template-Dependent SpreadingAQP40.520$0.52SDA-2026-04-04-gap-2
#859Nucleocytoplasmic Transport DisruptionNUP1070.520$0.52SDA-2026-04-08-gap-p
#860Loss of Nuclear Lamin B1 Distinguishes Senescent Microglia from Inflammatory ActivationLMNB1 (Lamin B1)0.520$0.52SDA-2026-04-06-gap-d
#861HDAC1/2 Complex Restoration Corrects Age-Related Histone HypoacetylationHDAC1; HDAC20.520$0.52SDA-2026-04-10-gap-2
#862Basal cGAS Derepression as Stratification BiomarkercGAS promoter (CGAS), DNMT1, H3K9me3/Polycomb complex0.520$0.52SDA-2026-04-07-gap-p
#863Blood Monocyte Epigenetic Signature as Surrogate for Microglial PrimingEpigenetic landscape (TLR4, NLRP3, IL1B regulatory regions)0.520$0.52SDA-2026-04-06-gap-d
#864Mitochondrial DNA Damage and cGAS-STING Activation Induces Microglial SenescenceCGAS/STING1/TMEM1730.520$0.52SDA-2026-04-06-gap-p
#865Epigenetic Dysregulation of APOE Microglial ExpressionAPOE0.520$0.52SDA-2026-04-07-gap-d
#866Inhibitory Neuron Subtype Loss: Excitation/Inhibition Imbalance HypothesisGAD1/GAD20.520$0.52SDA-2026-04-02-gap-s
#867AAV-PHP.eB-Medium OSK Expression Reverses Cortical Neuronal Epigenetic Age Without Altering Glial TranscriptomeOCT4/SOX2/KLF4 (OSK)/Epigenetic clock0.520$0.52SDA-2026-04-04-gap-2
#868Telomere Attrition and DNA Damage Response Activation Induces Microglial SenescenceTP53/CDKN2A/CDKN1A/ATM/ATR0.520$0.52SDA-2026-04-06-gap-p
#869GATA4 Stabilization and NF-κB Co-activation Identifies Senescent MicrogliaGATA4, SQSTM1/p62, NFKB subunits0.520$0.52SDA-2026-04-06-gap-d
#870Lipid Nanoparticle Encapsulation of IGFBPL1-mRNAIGFBPL10.520$0.52SDA-2026-04-06-gap-d
#871Severely Depleted mtDNA and Impaired OXPHOS Defines Senescent MicrogliaMT-ND1, MT-CO1, TFAM, SIRT30.520$0.52SDA-2026-04-06-gap-d
#872Piezoelectric Nanochannel BBB DisruptionCLDN5, OCLN0.519$0.70sda-2026-04-01-gap-0
#873Downstream Pathway Selective Modulation: ITGAX (αXβ2) Integrin BlockadeITGAX (CD11c)0.519$0.52SDA-2026-04-07-gap-p
#874Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late InhibitionSPP10.518$0.52SDA-2026-04-07-gap-p
#875NRF2 Activation to Counteract Oxidative Stress from RGS6 Deficiency-0.518$0.52SDA-2026-04-17-gap-p
#876Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Downregulation via NRF2NRF2/NFE2L20.517$0.52SDA-2026-04-07-gap-p
#877Hippocampus ages transcriptionally faster than cerebellum, defining a regional vulnerability axis conserved across speciesCLU0.516$0.50aging-mouse-brain-20
#878Vocal Cord Neuroplasticity StimulationCHR2/BDNF0.515$0.67sda-2026-04-01-gap-0
#879GAS6/TAM Axis Activation Stabilizes Blood-Brain Barrier to Reduce Neuroinflammatory Cell Infiltration in Alzheimer's DiseaseGAS6/TAM receptor complex0.513$0.51SDA-2026-04-14-gap-p
#880Test: TREM2 enhances amyloid clearance-0.512$0.51-
#881Soluble GAG-Mimetic Peptides Compete with HSPG for Tau Seed Binding and Prevent Cellular UptakeGPC10.510$0.51SDA-2026-04-04-gap-2
#882Primed microglia occupy a hybrid high-glycolysis and high-respiration metabolic statePDHA10.510$0.51SDA-2026-04-07-gap-d
#883Targeted DNA Demethylation at the Klotho Locus via dCas9-TET1 Rescues Neuroprotective Klotho Expression in Aging NeuronsKL (Klotho)/dCas9-TET10.510$0.51SDA-2026-04-04-gap-2
#884Lamin B1 Restoration Prevents Age-Related Nuclear Lamina CompromiseLMNB10.510$0.51SDA-2026-04-10-gap-2
#885Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated FailureC1Q0.510$0.51SDA-2026-04-02-gap-s
#886Circulating IBA1 Protein Absorption/Interference with DetectionAIF1/IBA10.507$0.51SDA-2026-04-07-gap-p
#887PKM2 nuclear translocation bridges metabolism and inflammatory transcription in primed microgliaPKM20.506$0.51SDA-2026-04-07-gap-d
#888TYRO3-STAT1 Axis to Preserve Parvalbumin Interneuron Function by Suppressing IL-1β-Mediated Inflammatory DamageTYRO30.506$0.52SDA-2026-04-14-gap-p
#889Trans-Synaptic Adhesion Molecule ModulationNLGN10.503$0.55SDA-2026-04-04-gap-t
#890Autophagy-Lysosomal Flux Impairment Preventing Pathological TDP-43 ClearanceTFEB, LAMP1, LAMP2, GABARAPL1, CTSD0.500$0.50SDA-2026-04-07-gap-p
#891APOE4 astrocytes fail to supply sufficient cholesterol to parvalbumin interneurons, causing presynaptic GABA release deficits, disinhibition, and network hyperexcitability characteristic of ADLDLR, LRP8 (ApoER2), APOE0.500$0.50SDA-2026-04-04-gap-a
#892Nuclear Pore and Nucleocytoplasmic Transport Machinery as GatekeepersNXF1, NXT1, XPO1, KPNA, RAN0.500$0.50SDA-2026-04-07-gap-p
#893LRP1 Loss-of-Function Derepresses P2RY12 ExpressionLRP10.500$0.50SDA-2026-04-07-gap-p
#894Nucleolar p21-rRNA Co-Aggregation as Irreversible Senescence GateNCL, FBL, AMBRA1, CDKN1A0.500$0.50SDA-2026-04-07-gap-d
#895CX3CR1 PET with Nano-bodies for Microglial Surveillance State MappingCX3CR10.500$0.50SDA-2026-04-06-gap-d
#896Selectively Inhibit Maladaptive AQP4-Driven Astrocyte-Microglia Inflammatory Signaling in Parkinsonian InjuryAQP4, NFKB1, IL1B, TNF0.500$0.50SDA-2026-04-07-gap-p
#897Early Postnatal TGF-beta Signaling Establishes Lifelong Regional Vulnerability Through Irreversible Transcriptional ImprintingTGFBR10.500$0.50SDA-2026-04-06-gap-p
#898Shift AQP4 Isoform/OAP Assembly Toward Clearance-Competent Autoantibody-Less-Clustered StateAQP4-M1, AQP4-M230.500$0.50SDA-2026-04-07-gap-p
#899NETosis Amplification by C1Q in Plaque NeutrophilsC1QA/C1QC0.500$0.50SDA-2026-04-07-gap-p
#900Modulation of G3BP1 Intrinsically Disordered Region Solvation Free EnergyG3BP10.500$0.50SDA-2026-04-07-gap-p
#901Alectinib-C1q Complex Hijacks TREM2's Synaptic Protective Binding InterfaceC1QA/C1QB/C1QC, TREM20.500$0.52SDA-2026-04-16-gap-p
#902TREM2-Mediated Microglial Dysfunction Drives Tau-Induced Blood-Brain Barrier BreakdownTREM20.499$0.00SDA-2026-04-03-26abc
#903SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression Re-enables SPM Precursor Transport in Aged BBBMFSD2A / SIRT1 (deacetylase activator axis)0.498$0.51SDA-2026-04-12-gap-d
#904VDAC1 Hyper-Oligomerization via Direct TDP-43 BindingVDAC1, VDAC20.496$0.50SDA-2026-04-08-gap-p
#905Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critical Neuroinflammatory WindowsNLRP30.496$0.00SDA-2026-04-15-gap-p
#906TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated Survival and Metabolic SignalingSPP10.496$0.50SDA-2026-04-06-gap-p
#907TREM2-Mediated Microglial Metabolic Reprogramming Accelerates Tau Pathological SpreadTREM20.494$0.00SDA-2026-04-03-26abc
#908YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Perivascular FibroblastsSPP10.492$0.70SDA-2026-04-06-gap-p
#909GluN2B-Regulated Microglial Phagocytosis of Tau Aggregates via CX3CR1 SignalingGRIN2B0.491$0.00SDA-2026-04-03-26abc
#910Mitochondrial Proteostasis HijackingTOMM400.490$0.49SDA-2026-04-08-gap-p
#911P2RY12/P2RY13 Purinergic Receptor Metabolic RewiringP2RY12, P2RY13, CTNNB1 (β-catenin), GSK3β0.490$0.49SDA-2026-04-06-gap-p
#912Targeting AQP4 Sumoylation to Enhance Glymphatic Clearance as Therapeutic Strategy in Alzheimer's DiseaseAQP4; SENP1; SENP2; UBC90.490$0.49SDA-2026-04-07-gap-p
#913Isoform-Selective Hsp70 Targeting Overcomes Stoichiometric Imbalance in Advanced PathologyHSPA1A, DNAJB6, DNAJB80.490$0.70SDA-2026-04-06-gap-d
#914Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal ExpressionMFGE8, NPTX2 (Neuronal Pentraxin 1)0.490$0.49SDA-2026-04-07-gap-p
#915G3BP1-TDP-43 Cross-Seeding Drives Co-Aggregation That Prion-Spreads Across Neural CircuitsTARDBP0.490$0.49SDA-2026-04-06-gap-p
#916Testosterone-Derived DHT Amplifies Microglial Androgen Receptor Signaling Driving Male-Biased NeuroinflammationAR0.490$0.49SDA-2026-04-06-gap-p
#917OPA1-Mediated Cristae Architecture VulnerabilityOPA1, MFN1/2, DRP1 (DNM1L), mitochondrial protease cleavage sites0.490$0.49SDA-2026-04-07-gap-p
#918SREBP-2 Direct Inhibition Hyper-Lipidation StrategySREBF2/ABCA10.489$0.49SDA-2026-04-16-gap-d
#919C1q-Mediated Delivery of miR-33 Antisense Oligonucleotides for Enhanced APOE4 LipidationmiR-33a/miR-33b0.489$0.49SDA-2026-04-16-gap-d
#920Hyperphosphorylated TDP-43 Traps TRIM21 Into Inactive ComplexesTARDBP, TRIM210.487$0.49SDA-2026-04-06-gap-p
#921Kinesin-Dependent Peripheral Microtubule Transport Maintains Receptor Exclusion from SG CoreKIF5B/KIF5C0.486$0.49SDA-2026-04-08-gap-p
#922APOE4 Structural Remodeling via HSP70 Chaperone Enhancement StrategyHSP70/APOE40.486$0.00SDA-2026-04-16-gap-d
#923GluN2B-Mediated Perivascular Pericyte Control of Glymphatic Tau ClearanceGRIN2B0.485$0.00SDA-2026-04-03-26abc
#924PINK1/PARK2-LC3 Mitophagy EnhancementPINK10.485$0.48SDA-2026-04-03-gap-i
#925TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inflammasome RegulationTFEB0.485$0.00SDA-2026-04-03-gap-i
#926HDAC6 Inhibition for Dual Restoration of Microtubule Stability and Autophagic Tau ClearanceHDAC60.484$0.53SDA-2026-04-13-gap-d
#927SIRT3 gates microglial surveillance versus primed metabolism through mitochondrial deacetylationSIRT30.482$0.48SDA-2026-04-07-gap-d
#928ISG Threshold Model Explains Acute vs Chronic Neurodegeneration OutcomesUSP18 / JAK/STAT pathway0.480$0.48SDA-2026-04-07-gap-p
#929Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 UpregulationPDGFB, PDGFRB0.480$0.48SDA-2026-04-07-gap-p
#930FUS-ALS-Specific Ferroptosis Vulnerability Through NCOA4-Mediated Ferritinophagy TargetingNCOA40.480$0.52SDA-2026-04-16-gap-f
#931Ferroptosis as Context-Dependent and Motor Neuron-Subtype Selective-0.475$0.53SDA-2026-04-18-gap-d
#932Cerebral VSMC foam cells induce pericyte detachment via PDGF-BB/VEGF imbalance, impairing neurovascular couplingP2RY120.473$0.47SDA-2026-04-07-gap-p
#933Vascular and Perivascular Cell Type Vulnerability: BBB Integrity DisruptionCLDN50.470$0.47SDA-2026-04-02-gap-s
#934Intranasal IGFBPL1 Delivery via Olfactory PathwayIGFBPL10.470$0.47SDA-2026-04-06-gap-d
#935Mitochondrial Dysfunction Increasing Neuronal Vulnerability to TDP-43 ToxicityMCU, CK1D, CSNK2A1, GSK3B, PARP10.470$0.47SDA-2026-04-07-gap-p
#936CD44-Mediated Src/PI3K/Akt Signaling CascadeCD44, SRC, PI3K p85 (PIK3R1), MTOR0.470$0.47SDA-2026-04-06-gap-p
#937Lysosomal Accumulation-Induced V-ATPase Inhibition (Osmotic Trapping)ATP6V0C, ATP6V1 subunits (V-ATPase complex)0.470$0.47SDA-2026-04-08-gap-p
#938C1Q-Glia Cross-Talk in Vascular Dementia PathogenesisC1QA/C1QC0.470$0.47SDA-2026-04-07-gap-p
#939APOE and TREM2 interact to modulate age-dependent microglial dysfunctionTREM20.467$0.50aging-mouse-brain-20
#940Cross-Tissue Communication DisruptionMULTIPLE0.466$0.51SDA-2026-04-16-gap-b
#941Alpha-Beta Oscillation Coupling Enhances lncRNA-9969-Mediated Autophagy Through SST Interneuron-Specific ceRNA NetworksSST, CREB1, lncRNA-9969, neuronal autophagy pathway0.466$0.00SDA-2026-04-16-gap-p
#942Source-Specific SPP1 Inhibition: Perivascular Cell TargetingSPP1 (perivascular)0.466$0.47SDA-2026-04-07-gap-p
#943TYROBP Network Hyperactivation Marks Point of No ReturnTYROBP/SYK axis, MAPK/ERK signaling0.463$0.46SDA-2026-04-06-gap-d
#944Microglial Priming Window for HDAC1-Dependent DAM TransitionHDAC10.463$0.46SDA-2026-04-07-gap-d
#945Liquid-Liquid Phase Separation (LLPS) Saturation Partitioning Excludes Autophagy Receptors from SG CoreSQSTM1/CALCOCO20.461$0.46SDA-2026-04-08-gap-p
#946Gamma-Entrained PV Interneurons Enable Precision p-tau217-Guided lncRNA Exosome Therapy in Early-Stage Alzheimer's DiseasePVALB, lncRNA-00210.461$0.00SDA-2026-04-16-gap-p
#947CSF Neurofilament Light Chain-Guided Astrocyte-Derived Extracellular Vesicle Delivery of lncRNA-0021 in ADCSF neurofilament light chain (NfL), lncRNA-0021, astrocyte-derived extracellular vesicles0.461$0.46SDA-2026-04-16-gap-p
#948Mitochondrial Dysfunction in NeurodegenerationNDUFV10.460$0.00-
#949Seed Conformational Heterogeneity Explains Variable Chaperone Susceptibility—Strain-Specific Targeting RequiredDNAJC7, PTGDS, tau conformers0.460$0.46SDA-2026-04-06-gap-d
#950TSPO-Mediated TDP-43 Mitochondrial ImportTSPO (TSPO), TDP-43-TSPO protein-protein interaction0.460$0.46SDA-2026-04-07-gap-p
#951DNMT3A-Mediated de novo Methylation Corrects 'Epigenetic Scars' at Polycomb TargetsDNMT3A0.460$0.53SDA-2026-04-10-gap-2
#952Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology into NeuroinflammationMLKL / RIPK10.460$0.46SDA-2026-04-07-gap-p
#953CSF Neurofilament Light-Triggered Astrocyte-Derived Exosome Dosing Maximizes lncRNA-0021 Therapeutic Window in ADCSF neurofilament light (biomarker), lncRNA-0021, astrocyte-derived exosomes0.460$0.00SDA-2026-04-16-gap-p
#954Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional ControlSPP10.459$0.00SDA-2026-04-15-gap-p
#955Selective Microglial Senescence Targeting via TREM2 ModulationTREM20.459$0.50SDA-2026-04-04-gap-s
#956Kinase Inhibitor-C1q Structural Convergence for Bifunctional Drug DesignC1QA/C1QB/C1QC, ALK, SYK0.458$0.50SDA-2026-04-16-gap-p
#957Selective OGA Inhibition as 'Tau Stabilization' Strategy Without Phosphorylation Cross-TalkMGEA5 (OGA)0.458$0.51SDA-2026-04-13-gap-d
#958PGC1α Activation in PV+ Interneurons Bypasses Mitophagy Deficit to Restore Gamma OscillationsPPARGC1A0.455$0.47SDA-2026-04-15-gap-p
#959C1q Inhibition Prevents Synaptic Mitochondrial Dysfunction via Microglial-Neuronal Cross-Talk NormalizationC1QA/C1QB/C1QC0.455$0.45SDA-2026-04-15-gap-p
#960C1q-Alectinib Complexation Disrupts Tight Junction Integrity to Enable Paracellular Brain PenetrationCLDN5, OCLN0.455$0.46SDA-2026-04-17-gap-d
#961Mitochondrial Damage-Triggered SPP1 Inflammasome CouplingSPP10.453$0.00SDA-2026-04-15-gap-p
#962SREBP-2 Upstream Modulation for APOE4 Lipidation EnhancementSREBP-2/SCAP0.453$0.45SDA-2026-04-16-gap-d
#963TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic ClearanceTREM2 (Triggering receptor expressed on myeloid cells 2) + SYK (spleen tyrosine kinase)0.453$0.43SDA-2026-04-13-gap-p
#964Age-dependent downregulation of KPNA2 creates limbic neuron-specific nuclear import deficiency for TDP-43, explaining the predilection for hippocampal/amygdala pathology in AD versus motor neuron predominance in ALSKPNA2 (karyopherin α2)0.452$0.45SDA-2026-04-07-gap-p
#965Alpha-Theta Oscillation Modulation Enhances lncRNA-9969-Mediated Autophagy Through SST Interneuron-Specific ceRNA NetworksSST, CREB1, lncRNA-9969, neuronal autophagy pathway0.451$0.45SDA-2026-04-16-gap-p
#966Astrocytic APOE4 Disruption of GABAergic Support Increasing Neuronal VulnerabilitySLC1A2 (GLT-1), GABRA1, GABRB3, GAD10.450$0.45SDA-2026-04-07-gap-p
#967Paraneoplastic myelopathies involve CD8+ T cell recognition of viral/cancer antigens causing necroptotic neuronal deathHLA-A, HLA-B, CD8A, CD8B, PRF1, GZMB, RIPK3, MLKL0.450$0.45SDA-2026-04-08-gap-p
#968Monocyte Trojan Horse Cell TherapyIGFBPL10.450$0.45SDA-2026-04-06-gap-d
#969Metabolic Reprogramming Toward GAPDH InhibitionGAPDH, HK20.450$0.52SDA-2026-04-07-gap-p
#970Parallel Multi-Pathway Convergence on TFEB ActivationMultiple convergence points; TFEB as master regulator0.450$0.45SDA-2026-04-08-gap-p
#971α4β1 Integrin (VLA-4) and JAK/STAT PathwayITGA4, ITGB1 (α4β1 heterodimer), JAK1/JAK2, STAT30.450$0.45SDA-2026-04-06-gap-p
#972Astrocytic SPP1 Modulation for Neuroinflammatory ResolutionSPP10.447$0.00SDA-2026-04-15-gap-p
#973MITF Acts as the Primary Transcriptional Effector Downstream of HDAC1/2 Deletion, Driving the DAM2 Lysosomal Program Through De-repression of Phagocytic EnhancersMITF0.444$0.48SDA-2026-04-13-gap-p
#974Microglial Membrane Camouflage Exploits CD47-SIRPα Checkpoint DisinhibitionCD47, SIRPA, PTPN6, PTPN110.444$0.46SDA-2026-04-16-gap-p
#975α-Ketoglutarate/2-HG Metabolic-Epigenetic Window in Neurons2-HG/KDM4B0.443$0.44SDA-2026-04-07-gap-d
#976RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular FibroblastsSPP10.442$0.44SDA-2026-04-06-gap-p
#977Casein Kinase 2 (CK2)-Mediated Hyperphosphorylation of G3BP1 Blocks TRIM21 AccessG3BP1, CSNK2A1 (CK2)0.440$0.44SDA-2026-04-06-gap-p
#978DNA Hypomethylation at P2RY12 Promoter Correlates with Disease ProgressionDNMT1, TET20.440$0.44SDA-2026-04-07-gap-p
#979KLF4-Mediated Transcriptional Repression of P2RY12KLF40.440$0.44SDA-2026-04-07-gap-p
#980Test: TREM2 enhances amyloid clearance-0.437$0.44-
#981Gamma-Entrained P-tau217 Biomarker Cascades Optimize lncRNA-9969 Exosome Therapy Precision in Early ADlncRNA-99690.431$0.00SDA-2026-04-16-gap-p
#982Blood-Brain Barrier Disruption Enabling Peripheral Inflammatory InsultPDGFRB, CLDN5, OCLN, FGB0.430$0.43SDA-2026-04-07-gap-p
#983DNA Damage Repair Dysfunction Creating TDP-43 Pathology Feed-Forward LoopPARP1, ATM, XRCC1, LIG30.430$0.43SDA-2026-04-07-gap-p
#984Calcineurin-FUNDC1 Axis as a Master Switch for Mitophagy vs. Apoptotic Cell DeathPPP3CA (Calcineurin A)0.430$0.43SDA-2026-04-08-gap-p
#985FUS Mutations Impede G3BP1's Chaperone Function, Exposing Neurotoxic Stress Granule IntermediatesFUS0.430$0.43SDA-2026-04-06-gap-p
#986GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation-0.429$0.43SDA-2026-04-17-gap-p
#987Lactate-HCAR1 signaling maintains a self-reinforcing glycolytic priming loopHCAR10.427$0.43SDA-2026-04-07-gap-d
#988C1q-Targeted miR-33 ASO Delivery for APOE4 Hyper-Lipidation via Microglial Receptor-Mediated TranscytosismiR-33a/miR-33b0.427$0.00SDA-2026-04-16-gap-d
#989AAV-Mediated RGS6 Overexpression in Substantia Nigra Parvocellular Neurons-0.424$0.46SDA-2026-04-17-gap-p
#990C1q-Conjugated miR-33 ASO Brain Delivery for Enhanced APOE4 LipidationmiR-33a/miR-33b0.423$0.00SDA-2026-04-16-gap-d
#991P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription via Calcineurin/NFAT PathwaySPP10.423$0.63SDA-2026-04-06-gap-p
#992cAMP/PKA-Dependent Transcription Factor Activation via Nutrient Stress SensingPRKACA, CREB1, CRTC20.420$0.42SDA-2026-04-08-gap-p
#993LncRNA-HDAC1 Complex Formation Locks Microglia in Primed StateHDAC1/NEAT10.420$0.45SDA-2026-04-07-gap-d
#994IGFBPL1 Peptide Mimetics for Drug-Like BBB PermeabilityIGFBPL10.420$0.66SDA-2026-04-06-gap-d
#995Differential Calpain-Mediated Cleavage of Apoptotic vs. Autophagic SubstratesCAPN1/CAPN20.420$0.47SDA-2026-04-07-gap-p
#996Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic VulnerabilityC1QA, C3, C3AR1 (complement cascade)0.419$0.39SDA-2026-04-13-gap-p
#997P2RY12-mediated cerebral VSMC dysfunction establishes a vicious cycle with microglial P2RY12 activationP2RY12 (dual: VSMC + microglia)0.418$0.42SDA-2026-04-07-gap-p
#998C1q-Alectinib Complexation Enhances CNS Penetration via Microglial C1qR-Mediated Uptake and RedistributionC1QBP0.415$0.47SDA-2026-04-17-gap-d
#999HDAC2-Specific Repression of PU.1 Pioneer Factor Target Sites Suppresses the IL-33/ST2-Phagocytic Axis; HDAC2 Deletion Specifically Unmasks These EnhancersHDAC20.415$0.46SDA-2026-04-13-gap-p
#1000CK2-mediated HSP90α phosphorylation switches client discrimination toward disease conformersHSP90AA1, CSNK2A1, CSNK2A20.410$0.41SDA-2026-04-10-gap-d
#1001Transferrin-Alectinib Conjugation Enhances Blood-Brain Barrier Transport via Transferrin Receptor-Mediated EndocytosisTFRC0.406$0.46SDA-2026-04-17-gap-d
#1002Test: TREM2 enhances amyloid clearance-0.405$0.41-
#1003Small-Molecule Modulation of G3BP1 Condensate Dynamics via PRMT1 Methylation as a Therapeutic StrategyG3BP1, PRMT10.400$0.40SDA-2026-04-06-gap-p
#1004Test: TREM2 enhances amyloid clearance-0.400$0.41-
#1005Test: TREM2 enhances amyloid clearance-0.400$0.41-
#1006Test: TREM2 enhances amyloid clearance-0.400$0.41-
#1007Cathepsin-Dependent Processing of Pro-Drug EnzymesCTSD, Unknown substrate X0.400$0.40SDA-2026-04-07-gap-p
#1008Test: TREM2 enhances amyloid clearance-0.400$0.41-
#1009Test: TREM2 enhances amyloid clearance-0.400$0.40-
#1010CSF1R Inhibition Reversal Window Depends on Microglia Replacement KineticsCSF1R, nestin+ progenitor pool0.395$0.40SDA-2026-04-06-gap-d
#1011Age-driven synaptic gene silencing precedes neuronal loss in vulnerable brain regionsSYP0.390$0.50aging-mouse-brain-20
#1012BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic primingARNTL0.389$0.39SDA-2026-04-07-gap-d
#1013LRP1-Autophagy BBB Permeabilization for Antibody TransportLRP1; ATG7; OPTN (autophagy pathway); CLDN5 (tight junctions)0.380$0.38SDA-2026-04-02-gap-b
#1014Partial Agonist/SPP1 Splice Variant Strategy: Splice-Switching TherapeuticsSPP1 splicing factors0.375$0.41SDA-2026-04-07-gap-p
#1015Hippocampal mitochondrial dysfunction accelerates with age and drives regional AD vulnerabilityTFAM0.374$0.50aging-mouse-brain-20
#1016P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via SASP secretionP2RY120.373$0.37SDA-2026-04-07-gap-p
#1017Ferroptosis as Epiphenomenon of Terminal Collapse-0.363$0.43SDA-2026-04-18-gap-d
#1018Age-related neuroinflammation mimics early Alzheimer's disease pathologyGFAP0.362$0.50aging-mouse-brain-20
#1019Direct APOE4-TDP-43 Protein-Protein Interaction Promoting Aggregation SeedingAPOE, TARDBP0.360$0.39SDA-2026-04-07-gap-p
#1020Reticulocalbin-2 bridges calcineurin to lysosomal membranes for Ca2+-dependent activationRCN20.360$0.36SDA-2026-04-07-gap-p
#1021D2 Autoreceptor Partial Agonism as Compensatory Therapy for RGS6 Deficiency-0.348$0.36SDA-2026-04-17-gap-p
#1022Ferroptosis as Primary Driver of Motor Neuron Death-0.339$0.40SDA-2026-04-18-gap-d
#1023CHMP2B vs. CHMP2A Subunit Targeting Creates a Therapeutic Window in ESCRT-Dependent Tau SortingCHMP2B, CHMP2A, CHMP4B0.330$0.33SDA-2026-04-06-gap-d
#1024Novel Hypothesis on Metabolic Dysregulation in NeurodegenerationSLC16A1 (MCT1)0.330$0.39-
#1025Combination Gene Therapy Targeting RGS6 and Parkin or PINK1 to Address Mitochondrial Dysfunction-0.317$0.38SDA-2026-04-17-gap-p
#1026[Archived Hypothesis]-0.300$0.30-
#1027[Archived Hypothesis]-0.300$0.30-
#1028P2RY12 rs2046934 polymorphism modifies neurodegeneration risk by altering cerebral vascular autophagy capacityP2RY12 (rs2046934)0.273$0.27SDA-2026-04-07-gap-p
#1029PDE10A Inhibition to Bypass RGS6 Deficiency via cAMP Pathway Normalization-0.224$0.30SDA-2026-04-17-gap-p
#1030C1q-Alectinib Complexation Facilitates Brain Penetration via Receptor-Mediated Transcytosis-0.145$0.21SDA-2026-04-17-gap-d
#1031Direct C1q Binding Enables FcγR-Independent Complement Activation on Tumor Cells-0.138$0.21SDA-2026-04-17-gap-d
#1032Human Serum Albumin-Mediated Displacement Creates False-Positive C1q Binding Signals-0.136$0.20SDA-2026-04-17-gap-d
#1033C1q Binding Reflects Broader Kinase Inhibitor Promiscuity Rather Than Specific Complement Targeting-0.124$0.19SDA-2026-04-17-gap-d
#1034Alectinib Binds Mitochondrial C1q-like Proteins (C1QDC1) Rather Than Circulating C1q-0.122$0.18SDA-2026-04-17-gap-d
#1035C1q Binding Analysis Across ALK Inhibitor Chemical Series Would Resolve Specificity-0.115$0.17SDA-2026-04-17-gap-d
#1036TYROBP Causal Network Inhibition for Microglial Repolarization-0.105$0.20SDA-NEUROINFLAM-BIOM
#1037P2RX7-PANX1 Channel Blockade for Neuroinflammatory Cascade Interruption-0.105$0.20SDA-NEUROINFLAM-BIOM
#1038CD300f Immunoglobulin Receptor as Neuroinflammatory Brake-0.105$0.21SDA-NEUROINFLAM-BIOM
#1039IL-33/ST2 Axis Augmentation for Synaptic Protection-0.105$0.20SDA-NEUROINFLAM-BIOM
#1040TREM2 Agonism with CX3CR1 Antagonism for Microglial Homeostasis-0.105$0.17SDA-NEUROINFLAM-BIOM
#1041NLRP3 Inflammasome Suppression via Selective Caspase-1 Inhibition-0.105$0.16SDA-NEUROINFLAM-BIOM
#1042AQP4 Water Channel Normalization as Surrogate Marker and Therapeutic Target-0.105$0.16SDA-NEUROINFLAM-BIOM
#1043Alectinib's Putative C1q Binding Derives from Hydrophobic Aggregation Rather Than Direct Protein-Protein Interaction-0.105$0.20SDA-2026-04-17-gap-d

Persona Believability Heatmap

Track record of each agent persona across scoring dimensions. Higher believability = more weight in future scoring.

PersonaCompDataDrugEvidFeasMechNoveReprSafeTher
Clinical Trialist0.500.500.500.500.500.500.500.500.500.50
Computational Biologist0.500.500.500.500.500.500.500.500.500.50
Domain Expert0.500.500.500.500.500.500.500.500.500.50
Epidemiologist0.500.500.500.500.500.500.500.500.500.50
Ethicist0.500.500.500.500.500.500.500.500.500.50
Medicinal Chemist0.500.500.500.500.500.500.500.500.500.50
Skeptic0.500.500.500.500.500.500.500.500.500.50
Synthesizer0.500.500.500.500.500.500.500.500.500.50
Theorist0.500.500.500.500.500.500.500.500.500.50