🔥 Neuroinflammation

Cross-disease microglial, astrocyte, and immune hypotheses

Index Score
0.477
Hypotheses
726
Unique Genes
465
Avg Score
0.638

Portfolio Strategy

This mission tracks 726 hypotheses targeting 465 unique genes. The portfolio index of 0.477 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 (726)

#HypothesisTargetScorePriceAnalysis
#1Closed-loop transcranial focused ultrasound with 40Hz gamma entrainment to restore hippocampal-cortical connectivity in early MCIPVALB1.000$0.96SDA-2026-04-03-26abc
#2Metabolic Reprogramming to Reverse SenescenceSIRT1,PGC1A,NAMPT1.000$0.98SDA-2026-04-04-gap-s
#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
#7PLCG2 Allosteric Modulation as a Precision Therapeutic for TREM2-Dependent Microglial DysfunctionPLCG20.941$0.82SDA-2026-04-01-gap-0
#8Closed-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
#9CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microglial Senescence ReversalCYP46A10.921$0.80SDA-2026-04-01-gap-l
#10Autophagy-Senescence Axis Therapeutic WindowATG7,BCL2,BCL2L10.921$0.93SDA-2026-04-04-gap-s
#11Selective Acid Sphingomyelinase Modulation TherapySMPD10.920$0.80SDA-2026-04-01-gap-l
#12HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM TransitionHK20.919$0.91SDA-2026-04-16-gap-d
#13Palmitoylethanolamide-Based Endocannabinoid TherapyPPARA0.919$0.80SDA-2026-04-16-gap-b
#14CYP46A1 Overexpression Gene TherapyCYP46A10.919$0.92SDA-2026-04-01-gap-l
#15SASP-Mediated Complement Cascade AmplificationC1Q/C30.910$0.93sda-2026-04-01-gap-0
#16TREM2-ASM Crosstalk in Microglial Lysosomal SenescenceSMPD10.910$0.79SDA-2026-04-03-gap-a
#17TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.907$0.81SDA-2026-04-03-gap-a
#18Nutrient-Sensing Epigenetic Circuit ReactivationSIRT10.907$0.83SDA-2026-04-04-gap-e
#19Closed-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
#20CSF1R Inhibition-Mediated Microglial Replacement as a State Transition ResetCSF1R0.898$0.85SDA-2026-04-16-gap-d
#21Closed-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
#22SIRT1-Mediated Reversal of TREM2-Dependent Microglial SenescenceSIRT10.895$0.83SDA-2026-04-03-gap-a
#23TREM2-Mediated Astrocyte-Microglia Crosstalk in NeurodegenerationTREM20.892$0.77SDA-2026-04-03-gap-a
#24Hypothesis 4: Metabolic Coupling via Lactate-Shuttling CollapseSLC16A1, SLC16A7, LDHA, PDHA10.892$0.84SDA-2026-04-16-gap-p
#25Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.888$0.91SDA-2026-04-01-gap-2
#26Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially IrreversibleAPP/PSEN1 (Aβ production), CHAT (cholinergic synthesis)0.887$0.81SDA-2026-04-12-20260
#27H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from Synapse Pruning to Amyloid ClearanceTREM20.887$0.90SDA-2026-04-12-gap-p
#28TREM2-APOE Axis Dissociation for Selective DAM ActivationTREM2-APOE axis0.886$0.86SDA-2026-04-01-gap-0
#29TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.880$0.92SDA-2026-04-03-gap-a
#30Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State Transition RestorationIFNG0.879$0.87SDA-2026-04-16-gap-d
#31TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.875$0.92SDA-2026-04-03-gap-a
#32TREM2-Mediated Cholesterol Dysregulation in Microglial SenescenceCYP46A10.869$0.89SDA-2026-04-03-gap-a
#33GluN2B-Mediated Thalamocortical Control of Glymphatic Tau ClearanceGRIN2B0.869$0.75SDA-2026-04-03-26abc
#34Complement Cascade Inhibition Synaptic Protection-0.867$0.81SDA-2026-04-16-gap-p
#35Closed-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
#36Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilizationBDNF0.861$0.81SDA-2026-04-03-26abc
#37Closed-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
#38TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM TransitionNAMPT0.858$0.74SDA-2026-04-16-gap-d
#39Senescent Cell ASM-Complement Cascade InterventionSMPD10.852$0.87SDA-2026-04-01-gap-l
#40Gamma entrainment therapy to restore hippocampal-cortical synchronySST0.851$0.79SDA-2026-04-03-26abc
#41APOE-Dependent Autophagy RestorationMTOR0.850$0.78sda-2026-04-01-gap-a
#42Microglial Senescence Prevention via TREM2/SASP Axis-0.847$0.78SDA-2026-04-16-gap-p
#43ACSL4-Driven Ferroptotic Priming in Disease-Associated MicrogliaACSL40.847$0.86SDA-2026-04-03-gap-s
#44TYROBP (DAP12) Conditional Antagonism for Early-Stage NeuroprotectionTYROBP0.844$0.72SDA-2026-04-01-gap-0
#45Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in NeurodegenerationSMPD30.844$0.87SDA-2026-04-01-gap-l
#46miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglial State TransitionMIR1550.843$0.82SDA-2026-04-16-gap-d
#47Circadian Glymphatic Entrainment via Targeted Orexin Receptor ModulationHCRTR1/HCRTR20.841$0.86sda-2026-04-01-gap-v
#48Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte SecretomeSST, SSTR1, SSTR20.839$0.92SDA-2026-04-16-gap-p
#49Sequential 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
#50Gamma Oscillation Enhancement Synergy-0.838$0.82SDA-2026-04-16-gap-p
#51Closed-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
#52Closed-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
#53Real-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
#54Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling for tau clearanceSST0.827$0.89SDA-2026-04-03-26abc
#55Microglial 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
#56Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.822$0.72SDA-2026-04-01-gap-2
#57Glymphatic-Mediated Tau Clearance DysfunctionMAPT0.821$0.85SDA-2026-04-03-26abc
#58Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservationBDNF0.820$0.70SDA-2026-04-03-26abc
#59Ketone Utilization Index as Metabolic Flexibility BiomarkerHMGCS20.819$0.83SDA-2026-04-04-gap-d
#60Extracellular Vesicle Biogenesis ModulationCHMP4B0.814$0.73SDA-2026-04-04-gap-t
#61AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue responsesPRKAA10.813$0.69sda-2026-04-01-gap-v
#62TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau ClearanceTREM20.812$0.86SDA-2026-04-03-26abc
#63CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerability ThresholdsAPOE, CLU0.811$0.69SDA-2026-04-15-gap-d
#64LRP1-Dependent Tau Uptake DisruptionLRP10.808$0.77SDA-2026-04-04-gap-t
#65CSF1R-TREM2 Co-Agonism for Sustained Microglial ExpansionCSF1R-TREM20.808$0.78SDA-2026-04-01-gap-0
#66Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to NeuroinflammationHCAR20.808$0.83SDA-2026-04-15-gap-d
#67P2RX7-Mediated Exosome Secretion BlockadeP2RX70.807$0.78SDA-2026-04-04-gap-t
#68Neutrophil Extracellular Trap (NET) InhibitionPADI40.806$0.74SDA-2026-04-16-gap-b
#69IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia InterfaceIL6R, IL60.806$0.74SDA-2026-04-13-gap-p
#70Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.805$0.78SDA-2026-04-01-gap-2
#71Calcium-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
#72TREM2-mTOR Co-Agonism for Metabolic ReprogrammingTREM2-mTOR pathway0.803$0.74SDA-2026-04-01-gap-0
#73Dual-Receptor Antibody Shuttling-0.803$0.87-
#74Prime Editing Precision Correction of APOE4 to APOE3 in MicrogliaAPOE0.803$0.68SDA-2026-04-03-gap-c
#75Mitochondrial DNA-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.803$0.68SDA-2026-04-01-gap-2
#76Targeting 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
#7740 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated MicrogliaACSL40.801$0.76SDA-2026-04-03-gap-s
#78TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism DysregulationTREM2/TYROBP0.800$0.72SDA-2026-04-06-gap-p
#79Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective EffectorMANF, CDNF0.798$0.73SDA-2026-04-16-gap-p
#80Microglial TREM2-SYK Pathway EnhancementTREM20.798$0.74SDA-2026-04-03-gap-s
#81SASP-Driven Microglial Metabolic Reprogramming in Synaptic PhagocytosisHK2/PFKFB30.796$0.94sda-2026-04-01-gap-0
#82Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)APOE0.795$0.75sda-2026-04-01-gap-0
#83Targeting SASP-Complement Amplification Through HIF-1α Downstream EffectorsC1QA, C1QB, C3, IL1B0.793$0.77SDA-2026-04-13-gap-p
#84Microglial-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.792$0.82SDA-2026-04-03-26abc
#85Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory PrimingTLR40.789$0.81SDA-2026-04-01-gap-2
#86VCP-Mediated Autophagy EnhancementVCP0.787$0.67SDA-2026-04-04-gap-t
#87Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid PathologyCHRNA7 (α7 nicotinic receptor), BACE10.785$0.81SDA-2026-04-12-20260
#88Competitive APOE4 Domain Stabilization PeptidesAPOE0.784$0.80sda-2026-04-01-gap-0
#89Integrated Biomarker Panel for Therapeutic Window IdentificationCHI3L10.784$0.67SDA-2026-04-15-gap-d
#90Senescent Microglia Resolution via Maresins-Senolytics CombinationBCL2L10.784$0.66sda-2026-04-01-gap-0
#91Closed-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
#92SASP-Driven Aquaporin-4 DysregulationAQP40.782$0.80sda-2026-04-01-gap-0
#93TREM2-mediated microglial tau clearance enhancementTREM20.780$0.67SDA-2026-04-04-gap-t
#94Sleep-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
#95ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter Degeneration in Alzheimer's DiseaseACSL40.779$0.82SDA-2026-04-03-gap-s
#96LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine in Disease-Associated MicrogliaLPCAT30.779$0.82SDA-2026-04-03-gap-s
#97Selective HDAC3 Inhibition with Cognitive EnhancementHDAC30.779$0.80SDA-2026-04-04-gap-e
#98SIRT1/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
#99ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE PeroxidationALOX150.777$0.82SDA-2026-04-03-gap-s
#100CX3CR1-TREM2 Integration for Synapse Pruning NormalizationCX3CR1-TREM20.776$0.76SDA-2026-04-01-gap-0
#101LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Disease-Associated MicrogliaLPCAT30.776$0.67SDA-2026-04-03-gap-s
#102Prefrontal sensory gating circuit restoration via PV interneuron enhancementPVALB0.775$0.79SDA-2026-04-03-26abc
#103Dual-Domain Antibodies with Engineered Fc-FcRn Affinity ModulationFCGRT0.773$0.79sda-2026-04-01-gap-0
#104Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory PathwayGPNMB, CD440.772$0.71SDA-2026-04-16-gap-p
#105LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Disease-Associated MicrogliaLPCAT30.770$0.66SDA-2026-04-03-gap-s
#106Oligodendrocyte Precursor Cell Senescence in White Matter DiseaseCSPG4,OLIG2,BCL20.769$0.73SDA-2026-04-04-gap-s
#107Chromatin Accessibility Restoration via BRD4 ModulationBRD40.768$0.79SDA-2026-04-04-gap-e
#108Lysosomal Cathepsin-Dependent Tau Clearance-0.767$0.75SDA-2026-04-16-gap-p
#109APOE4 Allosteric Rescue via Small Molecule ChaperonesAPOE0.765$0.79sda-2026-04-01-gap-0
#110SASP-Mediated Cholinergic Synapse DisruptionMMP2/MMP90.763$0.78sda-2026-04-01-gap-0
#111Circadian Clock-Autophagy SynchronizationCLOCK0.763$0.78sda-2026-04-01-gap-v
#112Hypothesis 3: HepaCAM-Containing Extracellular VesiclesHEPACAM1, HEPACAM20.762$0.67SDA-2026-04-16-gap-p
#113Cell-Type Specific TREM2 Upregulation in DAM MicrogliaTREM20.761$0.78analysis-SEAAD-20260
#114cGAS-STING Pathway Hyperactivation Mediates Tau PropagationcGAS (CGAS), STING (TMEM173)0.760$0.76SDA-2026-04-02-gap-2
#115APOE4 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
#116Targeted APOE4-to-APOE3 Base Editing TherapyAPOE0.758$0.78sda-2026-04-01-gap-0
#117INPP5D (SHIP1) Inhibition to Shift Microglial PolarizationINPP5D0.758$0.74SDA-2026-04-01-gap-0
#118sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy-0.757$0.87SDA-2026-04-16-gap-p
#119Multi-Modal Stress Response HarmonizationNR3C1/CRH/TNFA0.756$0.77sda-2026-04-01-gap-0
#120Senescence-Activated NAD+ Depletion RescueCD38/NAMPT0.755$0.77sda-2026-04-01-gap-0
#121Test: TREM2 enhances amyloid clearance-0.755$0.70-
#122Dual-Circuit Tau Vulnerability CascadeMAPT0.754$0.70SDA-2026-04-03-26abc
#123GFAP-Positive Reactive Astrocyte Subtype DelineationGFAP0.754$0.77analysis-SEAAD-20260
#124Enhancing Microglial Phagocytosis of Extracellular Tau via TREM2 ActivationTREM20.750$0.75SDA-2026-04-04-gap-t
#125TREM2-CSF1R Cross-Talk in Microglial Metabolic ReprogrammingTREM2, CSF1R0.748$0.90SDA-2026-04-03-gap-a
#126C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV Interneuron Input Elimination in Alzheimer's DiseaseC1QA, C1QB0.747$0.70SDA-2026-04-15-gap-d
#127Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT OverexpressionNAMPT0.745$0.81SDA-2026-04-04-gap-e
#128Circadian-Synchronized Proteostasis EnhancementCLOCK/ULK10.744$0.76sda-2026-04-01-gap-0
#129TREM2-SIRT1 Metabolic Senescence Circuit in Microglial AgingTREM20.744$0.90SDA-2026-04-03-gap-a
#130APOE Isoform Expression Across Glial SubtypesAPOE0.743$0.69analysis-SEAAD-20260
#131Smartphone-Detected Motor Variability CorrectionDRD2/SNCA0.742$0.69sda-2026-04-01-gap-0
#132Senescent Cell Mitochondrial DNA ReleaseCGAS/STING1/DNASE20.742$0.76sda-2026-04-01-gap-0
#133Near-infrared light therapy stimulates COX4-dependent mitochondrial motility enhancementCOX4I10.742$0.76sda-2026-04-01-gap-v
#134APOE4-Selective Lipid Nanoemulsion TherapyAPOE0.742$0.77sda-2026-04-01-gap-a
#135APOE-TREM2 Interaction ModulationTREM20.741$0.76sda-2026-04-01-gap-a
#136miR-33 Antisense Oligonucleotide Hyper-Lipidation StrategymiR-33/ABCA10.741$0.69SDA-2026-04-16-gap-d
#137Complement-SASP Amplification Cascade as Mechanistic LinkC1QA, C1QB, C3, IL1B, NFKB10.741$0.69SDA-2026-04-16-gap-p
#138Epigenetic Memory Erasure via TET2 ActivationTET20.741$0.76sda-2026-04-01-gap-0
#139TREM2-APOE4 Co-targeting — Simultaneous Correction of Lipid Sensing and Clearance DeficitsTREM2, APOE0.741$0.62SDA-2026-04-02-gap-0
#140STING Antagonists as ALS Therapeutics: Drug RepurposingSTING (TMEM173)0.740$0.66SDA-2026-04-07-gap-p
#141PARP1 Inhibition TherapyPARP10.738$0.76sda-2026-04-01-gap-0
#142SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy DysfunctionSIRT30.738$0.76SDA-2026-04-03-gap-s
#143Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor ImpairmentMAPT0.737$0.76SDA-2026-04-03-26abc
#144Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Antagonist in Tau PhaseTREM2, APOE, MAPT0.735$0.72SDA-2026-04-02-gap-0
#145Metabolic Inflexibility Precedes Transcriptional Reprogramming (NAD+/SIRT3 Axis)SIRT3/NAD+ salvage pathway, PGC-1α0.735$0.65SDA-2026-04-06-gap-d
#146TREM2 Agonism to Restore Microglial Phagocytosis Across Both PathologiesTREM2, TYROBP (DAP12), PLCG2, SYK0.735$0.68SDA-2026-04-16-gap-p
#147SGMS1-Driven Sphingomyelin Accumulation Impairs BACE1 Lysosomal Degradation via Autophagosome-Lysosome Fusion DysfunctionSGMS1, BECN10.734$0.72SDA-2026-04-15-gap-p
#148PDE4 Inhibition as Inflammatory Reset for PD OligodendrocytesPDE4A, PDE4B, PDE4D0.734$0.74SDA-2026-04-13-gap-p
#149Aquaporin-4 Polarization RescueAQP40.732$0.76sda-2026-04-01-gap-0
#150Senescence-Associated Myelin Lipid RemodelingPLA2G6/PLA2G4A0.732$0.75sda-2026-04-01-gap-0
#151Selective Neutral Sphingomyelinase-2 Inhibition TherapySMPD30.731$0.85SDA-2026-04-01-gap-l
#152Senescence-Induced Lipid Peroxidation SpreadingGPX4/SLC7A110.730$0.68sda-2026-04-01-gap-0
#153TREM2 Crosstalk and Synergistic Activation of Phagocytic TranscriptomeTREM2/DAP12 (TYROBP)0.730$0.73SDA-2026-04-06-gap-p
#154Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and NeurograninCHI3L1/TREM2/NRGN0.730$0.73SDA-2026-04-06-gap-d
#155Adenosine-Astrocyte Metabolic ResetADORA2A0.730$0.75sda-2026-04-01-gap-v
#156Phase-Separated Organelle TargetingG3BP10.729$0.75sda-2026-04-01-gap-0
#157Temporal SPP1 Inhibition During Critical WindowsSPP10.728$0.76SDA-2026-04-15-gap-p
#158Synthetic Biology BBB Endothelial Cell ReprogrammingTFR1, LRP1, CAV1, ABCB10.727$0.75sda-2026-04-01-gap-0
#159Metabolic Switch Targeting for A1→A2 RepolarizationHK20.726$0.75sda-2026-04-01-gap-0
#160Microglial TREM2-Complement Axis ModulationTREM2 and C30.726$0.75SDA-2026-04-03-gap-s
#161TFAM overexpression creates mitochondrial donor-recipient gradients for directed organelle traffickingTFAM0.725$0.75sda-2026-04-01-gap-v
#162Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)CD55 (DAF), CD46 (MCP)0.725$0.73SDA-2026-04-07-gap-p
#163Astrocyte-Mediated Neuronal Epigenetic RescueHDAC0.725$0.68SDA-2026-04-04-gap-e
#164Proteostasis Enhancement via APOE Chaperone TargetingHSPA1A0.724$0.75sda-2026-04-01-gap-a
#165TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN HyperactivationTBK10.724$0.71SDA-2026-04-13-gap-p
#166Microbial Inflammasome Priming PreventionNLRP3, CASP1, IL1B, PYCARD0.723$0.74SDA-2026-04-01-gap-2
#167Interfacial Lipid Mimetics to Disrupt Domain InteractionAPOE0.723$0.75sda-2026-04-01-gap-0
#168Circadian Rhythm Entrainment of Reactive AstrocytesBMAL10.722$0.75sda-2026-04-01-gap-0
#169Sleep Spindle-Synaptic Plasticity EnhancementCACNA1G0.721$0.75sda-2026-04-01-gap-v
#170Astroglial Gap Junction Coordination via Connexin-43 Phosphorylation ModulationGJA10.720$0.75sda-2026-04-01-gap-v
#171Excessive 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
#172AAV-PHP.eB-Mediated Microglial IGFBPL1 ExpressionIGFBPL10.720$0.72SDA-2026-04-06-gap-d
#173H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astrocyte SenescenceABCA1/ABCG1; LXR (NR1H3)0.720$0.72SDA-2026-04-06-gap-d
#174NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome PhenotypeNLRP3/CASP1/IL1B0.720$0.72SDA-2026-04-06-gap-p
#175Microglial IFN-β Priming of Motor Neuron cGAS/STING AmplificationIFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)0.720$0.72SDA-2026-04-07-gap-p
#176SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 RatioCXCL1, CXCL2, MMP30.720$0.72SDA-2026-04-06-gap-d
#177Stress Granule Phase Separation ModulatorsG3BP10.720$0.67sda-2026-04-01-gap-v
#178Magnetosonic-Triggered Transferrin Receptor ClusteringTFR10.719$0.75sda-2026-04-01-gap-0
#179Retinal Vascular Microcirculation RescuePDGFRB/ANGPT10.718$0.74sda-2026-04-01-gap-0
#180TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial Metabolic FitnessTREM2, TYROBP, SYK, PI3K0.718$0.70SDA-2026-04-02-gap-0
#181Disease-Associated Microglia Metabolic ReprogrammingTREM20.718$0.67SDA-2026-04-03-gap-s
#182APOE Isoform Conversion TherapyAPOE0.718$0.75sda-2026-04-01-gap-a
#183Engineered Apolipoprotein E4-Neutralizing Shuttle PeptidesAPOE, LRP1, LDLR0.718$0.74sda-2026-04-01-gap-0
#184Vascular-Glial Interface RestorationCLDN50.716$0.74SDA-2026-04-03-gap-s
#185Circadian-Synchronized LRP1 Pathway ActivationLRP1, MTNR1A, MTNR1B0.714$0.74sda-2026-04-01-gap-0
#186Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from InflammationTREM2, ADAM10, ADAM170.714$0.70SDA-2026-04-02-gap-0
#187Purinergic Signaling Polarization ControlP2RY1 and P2RX70.713$0.73sda-2026-04-01-gap-0
#188Test: TREM2 enhances amyloid clearance-0.712$0.70-
#189Circadian Glymphatic Rescue Therapy (Melatonin-focused)MTNR1A0.712$0.74sda-2026-04-01-gap-v
#190Early Proteasome Restoration TherapyPSMC0.712$0.66SDA-2026-04-03-gap-a
#191Noradrenergic-Tau Propagation BlockadeADRA2A0.711$0.74sda-2026-04-01-gap-v
#192APOE4-Specific Microglial Metabolic RescueAPOE, ABCA1, LDLR0.710$0.74SDA-2026-04-04-gap-n
#193HDAC3-Selective Inhibition for Clock ResetHDAC30.710$0.74sda-2026-04-01-gap-v
#194CSF YKL-40 as a Priming-Specific Chitinase MarkerCHI3L1/YKL-400.710$0.71SDA-2026-04-06-gap-d
#195Microglial Disease-Associated States: TREM2-Independent Pathways Driving NeuroinflammationAPOE0.710$0.71SDA-2026-04-02-gap-s
#196H4: Senomorphic Compounds Preserve Astrocyte Function While Reversing SenescenceMTOR; MEGF10; MERTK0.710$0.71SDA-2026-04-06-gap-d
#197Selective 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
#198Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in Alzheimer's DiseaseTREM20.710$0.71SDA-2026-04-06-gap-p
#199Metabolic Circuit Breaker via Lipid Droplet ModulationPLIN20.709$0.74sda-2026-04-01-gap-0
#200Autophagosome Maturation Checkpoint ControlSTX170.709$0.74sda-2026-04-01-gap-0
#201Matrix Stiffness Normalization via Targeted Lysyl Oxidase InhibitionLOX/LOXL1-40.709$0.73sda-2026-04-01-gap-v
#202TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to RestorativeTREM20.708$0.71SDA-2026-04-07-gap-p
#203Membrane Cholesterol Gradient ModulatorsABCA1/LDLR/SREBF20.708$0.73SDA-2026-04-01-gap-l
#204Orexin-Microglia Modulation TherapyHCRTR20.707$0.74sda-2026-04-01-gap-v
#205Creatine Kinase System Capacity as Neural Energy Reserve BiomarkerCKB0.707$0.70SDA-2026-04-04-gap-d
#206TET2-Mediated Demethylation Rejuvenation TherapyTET20.706$0.73sda-2026-04-01-gap-v
#207Autophagy-Lysosomal Degradation of IBA1 in Stressed MicrogliaLC3/P62/SQSTM10.706$0.71SDA-2026-04-07-gap-p
#208Lysosomal Enzyme Trafficking CorrectionIGF2R0.706$0.73sda-2026-04-01-gap-0
#209Endothelial Glycocalyx Regeneration via Syndecan-1 UpregulationSDC10.705$0.73sda-2026-04-01-gap-v
#210Test: TREM2 enhances amyloid clearance-0.705$0.70-
#211Ferroptosis Inhibition for α-Synuclein NeuroprotectionGPX40.705$0.73SDA-2026-04-03-gap-a
#212Microglial Efferocytosis Enhancement via GPR32 SuperagonistsCMKLR10.704$0.73sda-2026-04-01-gap-0
#213Astrocyte-Neuron Metabolic Coupling TitrationBDH10.704$0.70SDA-2026-04-03-gap-d
#214Multiplexed Base Editing for Simultaneous Neuroprotective Gene ActivationSOD1, TARDBP, BDNF, GDNF, IGF-10.704$0.74SDA-2026-04-03-gap-c
#215TLR4/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
#216Purinergic P2Y12 Inverse Agonist TherapyP2RY120.703$0.73sda-2026-04-01-gap-v
#217Microglial Exosome-Mediated Tau PropagationMAPT0.702$0.67SDA-2026-04-03-26abc
#218Mitochondrial-Nuclear Epigenetic Cross-Talk RestorationSIRT30.701$0.73SDA-2026-04-04-gap-e
#219DAMP-Scavenging Microglial ResetHMGB1, S100 proteins0.701$0.73SDA-2026-04-04-gap-n
#220Microglial Purinergic ReprogrammingP2RY120.701$0.73sda-2026-04-01-gap-0
#221Transglutaminase-2 Cross-Linking Inhibition StrategyTGM20.701$0.73sda-2026-04-01-gap-9
#222Targeted Butyrate Supplementation for Microglial Phenotype ModulationGPR109A0.700$0.73SDA-2026-04-01-gap-2
#223TREM2 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
#224SCFA-Producing Bacterial Depletion → Loss of Neuroprotective MicroenvironmentHDAC3, GPR41 (FFAR3), GPR43 (FFAR2), Nrf2, HMOX10.700$0.70sda-2026-04-01-gap-2
#225AAV-Mediated APOE2/APOE3 Gene Delivery to Convert APOE GenotypeAPOE0.700$0.70SDA-2026-04-02-gap-a
#226NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward SenescenceSIRT1/NAMPT/PPARGC1A0.700$0.70SDA-2026-04-06-gap-p
#227Metabolic 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
#228Mechanosensitive Ion Channel ReprogrammingPIEZO1 and KCNK20.700$0.72sda-2026-04-01-gap-0
#229TREM2-Mediated Selective Aggregate Clearance PathwayTREM20.699$0.73sda-2026-04-01-gap-9
#230H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective EffectorPXR (NR1I2), IDO10.699$0.70SDA-2026-04-15-gap-p
#231Granzyme B Inhibition with Serpina3n to Preserve Axonal Integrity Against Cytotoxic AttackGZMB0.698$0.73SDA-2026-04-15-gap-d
#232TFEB-Independent Autophagy BypassULK10.697$0.65SDA-2026-04-03-gap-d
#233Lysosomal Calcium Channel Modulation TherapyMCOLN10.697$0.73sda-2026-04-01-gap-0
#234Perforant Path Presynaptic Terminal Protection StrategyPPARGC1A0.696$0.72sda-2026-04-01-gap-0
#235Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated AmplificationMAPT0.696$0.73SDA-2026-04-03-26abc
#236Axonal RNA Transport ReconstitutionHNRNPA2B10.695$0.73sda-2026-04-01-gap-v
#237Mitochondrial Transfer Pathway EnhancementMIRO10.695$0.73sda-2026-04-01-gap-0
#238Temporal Microglial State SwitchingOptogenetic constructs, ion channels0.695$0.73SDA-2026-04-04-gap-n
#239Complement C1q Mimetic Decoy TherapyC1QA0.695$0.72sda-2026-04-01-gap-v
#240Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene TherapyALOX150.695$0.72sda-2026-04-01-gap-0
#241Palmitoylation-Targeted BACE1 Trafficking DisruptorsBACE10.693$0.73SDA-2026-04-01-gap-l
#242Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial LossCCR20.693$0.69SDA-2026-04-07-gap-p
#243Astrocytic Connexin-43 Upregulation Enhances Neuroprotective Mitochondrial DonationGJA10.692$0.72sda-2026-04-01-gap-2
#244Ocular Immune Privilege ExtensionFOXP3/TGFB10.692$0.72sda-2026-04-01-gap-0
#245Sphingomyelin Synthase Activators for Raft RemodelingSGMS1/SGMS20.692$0.72SDA-2026-04-01-gap-l
#246TREM2-Dependent Microglial Surveillance Controls AQP4-Mediated Tau Clearance Through Astrocytic Endfoot MaintenanceTREM20.691$0.74SDA-2026-04-03-26abc
#247TREM2-Mediated Microglial Dysfunction Disrupts Oligodendrocyte Tau Clearance NetworksTREM20.691$0.74SDA-2026-04-03-26abc
#248cGAS-STING Senescence Circuit DisruptionCGAS, STING10.691$0.72SDA-2026-04-03-gap-a
#249Extracellular Matrix Stiffness ModulationPIEZO10.691$0.72sda-2026-04-01-gap-0
#250Epigenetic Memory Reprogramming via CRISPRa-Mediated Chromatin RemodelingSIRT1, FOXO3, NRF2, TFAM0.690$0.72SDA-2026-04-03-gap-c
#251TREM2 Agonism to Rescue APOE4-Induced Microglial DysfunctionTREM20.690$0.69SDA-2026-04-02-gap-a
#252TREM2-Dependent Microglial State Transition as Therapeutic Window in Alzheimer's DiseaseTREM2, SYK signaling pathway0.690$0.69SDA-2026-04-02-gap-2
#253Loss of AQP4 Polarization Impairs Glymphatic Perivascular Influx, Causing Metabolite AccumulationAQP40.690$0.69SDA-2026-04-07-gap-p
#254Astrocyte Reactivity Heterogeneity with APOE4-Dependent VulnerabilityAPOE0.690$0.69SDA-2026-04-02-gap-s
#255Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GRNGRN, SLC16A3 (MCT4)0.690$0.69SDA-2026-04-02-gap-2
#256Rab27A/B-mediated exosomal tau secretion from microglia drives frontal cortex propagation at Braak III-VIRAB27A0.690$0.69SDA-2026-04-07-gap-d
#257H5: BET Bromodomain Readers Sense Aberrant Chromatin and Drive Neuroinflammatory TranscriptionBRD4, BET bromodomains (BRD2/3/4)0.690$0.69SDA-2026-04-04-gap-2
#258Ganglioside Rebalancing TherapyST3GAL2/ST8SIA10.690$0.72SDA-2026-04-01-gap-l
#259Endothelial 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
#260Reelin-Mediated Cytoskeletal Stabilization ProtocolRELN0.689$0.72sda-2026-04-01-gap-0
#261Cross-Seeding Prevention StrategyTARDBP0.689$0.72sda-2026-04-01-gap-v
#262Hypocretin-Neurogenesis Coupling TherapyHCRT0.688$0.72sda-2026-04-01-gap-v
#263Lysosomal Positioning Dynamics ModulationLAMP10.686$0.72sda-2026-04-01-gap-0
#264CX43 hemichannel engineering enables size-selective mitochondrial transferGJA10.686$0.72sda-2026-04-01-gap-v
#265TREM2 Conformational Stabilizers for Synaptic DiscriminationTREM20.685$0.72sda-2026-04-01-gap-v
#266Pericyte Contractility Reset via Selective PDGFR-β AgonismPDGFRB0.684$0.72sda-2026-04-01-gap-v
#267Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance FateAHR, IL10, TNFRSF13B, TIGIT, FOXP30.683$0.68SDA-2026-04-13-gap-p
#268Astrocyte-Selective APOE4 Silencing via Lipid NanoparticlesAPOE40.682$0.70SDA-2026-04-03-gap-d
#269Context-Dependent CRISPR Activation in Specific Neuronal SubtypesCell-type-specific essential genes0.682$0.71SDA-2026-04-03-gap-c
#270Flotillin-1 Stabilization CompoundsFLOT10.681$0.71SDA-2026-04-01-gap-l
#271CRISPR-Mediated Mitochondrial Genome Editing for Complex I DysfunctionMT-ND1, MT-ND4, MT-ND60.681$0.72SDA-2026-04-03-gap-c
#272R-Loop Resolution Enhancement TherapySETX0.680$0.71sda-2026-04-01-gap-v
#273Chaperone-Mediated APOE4 Refolding EnhancementHSPA1A, HSP90AA1, DNAJB1, FKBP50.680$0.70sda-2026-04-01-gap-0
#274Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid PlexusAQP10.680$0.71sda-2026-04-01-gap-v
#275Oligodendrocyte Protectin D1 Mimetic for Myelin ResolutionGPR370.680$0.71sda-2026-04-01-gap-0
#276Glial Neuroinflammatory Amplification by TDP-43 PathologyTARDBP0.680$0.68SDA-2026-04-08-gap-p
#277AQP4 Dysregulation Promotes Neuroinflammation Through Impaired CNS-Peripheral Immune Interface FunctionAQP4; IL6R; CD46 (complement)0.680$0.68SDA-2026-04-07-gap-p
#278CSF Soluble TREM2 Fragment Ratio as Priming State IndicatorTREM2/ADAM10/170.680$0.68SDA-2026-04-06-gap-d
#279Synaptic Phosphatidylserine Masking via Annexin A1 MimeticsANXA10.680$0.71sda-2026-04-01-gap-v
#280GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis BlockadeGPX40.680$0.65SDA-2026-04-16-gap-f
#281Complement C1QA Spatial Gradient in Cortical LayersC1QA0.678$0.70analysis-SEAAD-20260
#282Dynamic Lactate-Pyruvate Ratio as Therapeutic Stratification BiomarkerSLC16A10.677$0.67SDA-2026-04-04-gap-d
#283Cell-Type Specific TFEB ModulationTFEB0.677$0.70SDA-2026-04-03-gap-d
#284Astrocyte-Mediated Microglial Memory ErasureGFAP, S100B0.677$0.71SDA-2026-04-04-gap-n
#285Selective Tau Kinase Inhibition in Vulnerable Neuronal SubtypesMAPT0.676$0.71SDA-2026-04-03-gap-s
#286Microglial TREM2-Mediated Tau Phagocytosis ImpairmentMAPT0.676$0.72SDA-2026-04-03-26abc
#287White Matter Oligodendrocyte Protection via CXCL10 InhibitionCXCL100.675$0.70SDA-2026-04-03-gap-a
#288Excitatory Neuron Vulnerability via SLC17A7 DownregulationSLC17A70.675$0.70analysis-SEAAD-20260
#289RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo deliveryRAB27A0.674$0.71sda-2026-04-01-gap-v
#290Metabolic Reprogramming via Microglial Glycolysis InhibitionHK20.672$0.71sda-2026-04-01-gap-v
#291FOXO3-Longevity Pathway Epigenetic ReprogrammingFOXO30.672$0.71sda-2026-04-01-gap-v
#292Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.672$0.72SDA-2026-04-03-26abc
#293TREM2 R47H Metabolic Lock-in at Cholesterol Ester AccumulationTREM2/ACAT1/LXR0.672$0.70SDA-2026-04-15-gap-d
#294Partial Neuronal Reprogramming via Modified Yamanaka CocktailOCT40.672$0.70SDA-2026-04-04-gap-e
#295Age-Dependent Complement C4b Upregulation Drives Synaptic Vulnerability in Hippocampal CA1 NeuronsC4B0.671$0.70SDA-2026-04-03-gap-a
#296LPS-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
#297TREM2 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
#298AQP4-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
#299Microglial P2Y12-Dependent Territorial Segregation of Synaptic InputsP2RY12 (P2Y12 receptor)0.670$0.67SDA-2026-04-07-gap-p
#300Restore AQP4 Perivascular Polarization by Stabilizing DAPC/SNTA1/DAG1 Anchoring ComplexAQP4, SNTA1, DAG10.670$0.67SDA-2026-04-07-gap-p
#301Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory CommunicationCHRNA70.669$0.70SDA-2026-04-01-gap-2
#302Astrocyte MCT1/MCT4 Ratio Disruption with Metabolic UncouplingSLC16A10.668$0.70SDA-2026-04-03-gap-s
#303TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition CheckpointTREM2, SYK signaling axis0.668$0.67SDA-2026-04-06-gap-d
#304Heat Shock Protein 70 Disaggregase AmplificationHSPA1A0.668$0.70sda-2026-04-01-gap-0
#305Aquaporin-4 Polarization Enhancement via TREK-1 Channel ModulationKCNK20.668$0.70sda-2026-04-01-gap-v
#306Mitochondrial-Lysosomal Contact Site EngineeringRAB7A0.668$0.70sda-2026-04-01-gap-0
#307SIRT6-NAD+ Axis Enhancement TherapySIRT60.667$0.70sda-2026-04-01-gap-v
#308White Matter Vulnerability Prevention via Oligodendrocyte ProtectionCXCL100.667$0.70SDA-2026-04-03-gap-a
#309Lipid Droplet Dynamics as Phenotype SwitchesDGAT1 and SOAT10.666$0.70sda-2026-04-01-gap-0
#310GAP43-mediated tunneling nanotube stabilization enhances neuroprotective mitochondrial transferGAP430.666$0.70sda-2026-04-01-gap-v
#311Glymphatic-Cholinergic Tau Clearance CascadeMAPT0.666$0.70SDA-2026-04-03-26abc
#312EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.665$0.70sda-2026-04-12-ev-ad
#313Lactate/Pyruvate Ratio Dynamics in CSF as a Neuroinflammation-Metabolism Interface BiomarkerLDHA, TREM20.665$0.70SDA-2026-04-04-SDA-2
#314Oligodendrocyte DNA Repair Enhancement TherapyPARP1 and XRCC10.665$0.70SDA-2026-04-03-gap-s
#315Complement C1q Subtype SwitchingC1QA0.665$0.70sda-2026-04-01-gap-0
#316Gut Barrier Permeability-α-Synuclein Axis ModulationCLDN1, OCLN, ZO1, MLCK0.663$0.69SDA-2026-04-01-gap-2
#317TNF-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
#318Sphingolipid Metabolism ReprogrammingCERS20.663$0.70sda-2026-04-01-gap-0
#319RNA Granule Nucleation Site ModulationG3BP10.662$0.70sda-2026-04-01-gap-0
#320Circadian-Metabolic Microglial ReprogrammingCLOCK, BMAL1, PER20.662$0.69SDA-2026-04-04-gap-n
#321Peripheral-Central Immune Decoupling TherapyTREM2, complement cascade components0.662$0.69SDA-2026-04-04-gap-n
#322EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.661$0.71sda-2026-04-12-ev-ad
#323Biorhythmic Interference via Controlled Sleep OscillationsGABRA10.661$0.70sda-2026-04-01-gap-0
#324Astrocyte IL-1β as Paracrine Mediator of Microglial Complement ExpressionIL1B; IL1R1; MYD880.660$0.66SDA-2026-04-08-gap-p
#325BBB Integrity Loss Defines Absolute Therapeutic Window ClosureMMP-9, Claudin-5, PDGFRβ (pericyte coverage)0.660$0.66SDA-2026-04-06-gap-d
#326Focused Ultrasound with Microbubble Contrast AgentsIGFBPL10.660$0.66SDA-2026-04-06-gap-d
#327Chronic 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
#328Vagal Afferent Microbial Signal ModulationGLP1R, BDNF0.660$0.69SDA-2026-04-01-gap-2
#329Complement C1QA Inhibition Synergizes with PV Interneuron ModulationC1QA, PVALB0.659$0.65SDA-2026-04-13-gap-p
#330TREM2 Activation as an Amplification Node for R136S ProtectionTREM20.657$0.65SDA-2026-04-13-gap-p
#331NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP AmplificationNLRP30.657$0.69SDA-2026-04-12-gap-d
#332Temporal TET2-Mediated Hydroxymethylation CyclingTET20.657$0.70SDA-2026-04-04-gap-e
#333Liquid-Liquid Phase Separation Modifier TherapyG3BP10.656$0.69sda-2026-04-01-gap-9
#334Mitochondrial RNA Granule Rescue PathwaySYNCRIP0.656$0.69sda-2026-04-01-gap-v
#335Time-Dependent BBB Repair StrategyMULTIPLE0.656$0.70SDA-2026-04-16-gap-b
#336Optogenetic Microglial Deactivation via Engineered Inhibitory OpsinsCX3CR10.655$0.70sda-2026-04-01-gap-v
#337Astrocyte-Microglia Communication Rebalancing via Cytokine ModulationIL1A, TNF, C1Q0.655$0.69SDA-2026-04-03-gap-d
#338Test: TREM2 enhances amyloid clearance-0.655$0.66-
#339Arginine Methylation Enhancement TherapyPRMT10.653$0.69sda-2026-04-01-gap-0
#340KDM6A-Mediated H3K27me3 RejuvenationKDM6A0.653$0.69sda-2026-04-01-gap-v
#341Nucleolar Stress Response NormalizationNPM10.653$0.69sda-2026-04-01-gap-v
#342Locus Coeruleus-Hippocampal Circuit ProtectionMAPT0.653$0.67SDA-2026-04-03-26abc
#343The Mitochondrial-Lysosomal Metabolic Coupling DysfunctionTFEB0.652$0.69SDA-2026-04-02-gap-v
#344SUMO1-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
#345Microbiota-Microglia Axis ModulationMultiple0.651$0.68SDA-2026-04-04-gap-2
#346Astrocyte APOE4-Specific Lipid Metabolism CorrectionAPOE0.651$0.69SDA-2026-04-03-gap-s
#347Prohibitin-2 Mitochondrial Cross-Seeding Hub DisruptionPHB20.650$0.69sda-2026-04-01-gap-9
#348Mitochondrial Calcium Buffering Enhancement via MCU ModulationMCU0.650$0.69sda-2026-04-01-gap-0
#349NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Antioxidant DefenseNRF2 (NFE2L2), KEAP10.650$0.62SDA-2026-04-16-gap-f
#350Pharmacologically Boost AQP4X Readthrough to Restore Perivascular ClearanceAQP4, AQP4X0.650$0.65SDA-2026-04-07-gap-p
#351Loss of Homeostatic Epigenetic Identity Reprograms Microglia to Dystrophic StateEZH2/DNMT1/DNMT3A/P2RY12/TMEM1190.650$0.65SDA-2026-04-06-gap-p
#352Galectin-3 deletion attenuates NLRP3 inflammasome activation downstream of lysosomal membrane permeabilizationLGALS30.650$0.65SDA-2026-04-04-gap-l
#353NeuroD1-Mediated Astrocyte Reprogramming Attenuates Neuroinflammation Through Epigenetic Remodeling of A1 Astrocyte Signature GenesNeuroD1/NF-kB0.650$0.65SDA-2026-04-04-gap-2
#354TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCsRELA (p65), IKBKB (IKKβ)0.650$0.65SDA-2026-04-07-gap-p
#355APOE-Mediated Synaptic Lipid Raft StabilizationSPTLC10.649$0.68sda-2026-04-01-gap-a
#356Glycosaminoglycan Template Disruption ApproachHSPG20.649$0.68sda-2026-04-01-gap-9
#357Glial Glycocalyx Remodeling TherapyHSPG20.649$0.69sda-2026-04-01-gap-0
#358APOE-TREM2 Ligand Availability Dysfunction in NeurodegenerationAPOE0.649$0.64SDA-2026-04-03-gap-a
#359TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling in White Matter NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#360TREM2-Mediated Mitochondrial Dysfunction in NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#361Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading to Senescent Glial NetworksTREM20.649$0.64SDA-2026-04-03-gap-a
#362Apoptosis-Senescence Decision Point InterventionTP53,BAX,BAK1,CASP30.649$0.68SDA-2026-04-04-gap-s
#363IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage ReprogrammingIL10, CSF1R, CD400.648$0.65SDA-2026-04-13-gap-p
#364CLU-APOE-TREM2 Tripartite Axis as a Coordinate Therapeutic TargetCLU-APOE-TREM2 axis (LXR/RXR pathway)0.648$0.64SDA-2026-04-14-gap-p
#365DNMT1-Targeting Antisense Oligonucleotide ResetDNMT10.648$0.69sda-2026-04-01-gap-v
#366Mitochondrial SPM Synthesis Platform EngineeringALOX50.647$0.69sda-2026-04-01-gap-0
#367Epigenetic Reprogramming of Microglial MemoryDNMT3A, HDAC1/20.647$0.68SDA-2026-04-04-gap-2
#368Inflammatory State-Dependent Ketone TimingIRAKM0.647$0.64SDA-2026-04-03-gap-d
#369Grid Cell-Specific Metabolic Reprogramming via IDH2 EnhancementIDH20.646$0.69sda-2026-04-01-gap-0
#370Astrocyte Metabolic Memory ReprogrammingSIRT10.646$0.64SDA-2026-04-04-gap-d
#371NLRP3/Mitophagy Coupling ModulationNLRP30.646$0.67SDA-2026-04-03-gap-i
#372Synthetic Biology Rewiring via Orthogonal ReceptorsCNO0.645$0.69sda-2026-04-01-gap-0
#373Miro1-Mediated Mitochondrial Trafficking Enhancement TherapyRHOT10.645$0.68sda-2026-04-01-gap-2
#374Ephrin-B2/EphB4 Axis ManipulationEPHB40.645$0.68sda-2026-04-01-gap-0
#375Oligodendrocyte Remyelination EnhancementTREM20.644$0.67SDA-2026-04-03-gap-a
#376Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy-0.644$0.63SDA-2026-04-15-gap-p
#377White Matter Immune Checkpoint RestorationCXCL100.644$0.68SDA-2026-04-03-gap-a
#378Cell-Type Specific Metabolic ReprogrammingPPARA0.643$0.68SDA-2026-04-03-gap-s
#379Epigenetic Silencing of AIF1 Gene Locus by Chronic InflammationDNMT1/DNMT3A0.643$0.64SDA-2026-04-07-gap-p
#380TREM2-Driven Senescence Biomarker Index for Predicting Neurodegeneration RiskTREM20.642$0.64SDA-2026-04-03-gap-a
#381Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-SeedingCSGA0.642$0.68SDA-2026-04-01-gap-2
#382RNA-Binding Competition Therapy for TDP-43 Cross-SeedingTARDBP0.642$0.68sda-2026-04-01-gap-9
#383Glycine-Rich Domain Competitive InhibitionTARDBP0.640$0.68sda-2026-04-01-gap-0
#384CX3CR1 Promoter Methylation Disrupts Neuron-Microglia Cross-TalkCX3CR10.640$0.64SDA-2026-04-07-gap-d
#385C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque MacrophagesC1QA/C1QC0.640$0.64SDA-2026-04-07-gap-p
#386Colonic 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
#387Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progressionGFAP0.640$0.68SDA-2026-04-04-analy
#388Mitochondrial NAD+ Salvage EnhancementSTING10.639$0.67SDA-2026-04-03-gap-a
#389Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelopmental FormsSOD1, HTT, TARDBP0.638$0.67SDA-2026-04-03-gap-c
#390Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid PhaseTREM20.637$0.62SDA-2026-04-02-gap-0
#391Test: TREM2 enhances amyloid clearance-0.637$0.64-
#392Vascular mural cell degeneration precedes and exacerbates parenchymal pathologyPDGFRB0.637$0.66SDA-2026-04-04-analy
#393Astrocyte Metabolic Reprogramming via APOE4 CorrectionAPOE0.636$0.67SDA-2026-04-03-gap-s
#394TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection FilterTREM20.636$0.62SDA-2026-04-15-gap-d
#395HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.634$0.68SDA-2026-04-04-gap-t
#396C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic LoopC3AR1, C3, NFKB10.633$0.65SDA-2026-04-14-gap-p
#397Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1STAT3/JAK10.633$0.63SDA-2026-04-07-gap-p
#398HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding InhibitorDNAJB60.632$0.67sda-2026-04-01-gap-9
#399TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk AlleleTREM20.631$0.61SDA-2026-04-02-gap-0
#400Gap Junction Hemichannel Modulation for Controlled Mitochondrial ExchangePANX10.631$0.67sda-2026-04-01-gap-2
#401Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoot Repair in NMOSDAQP4, IL6R, CD19, C50.630$0.63SDA-2026-04-07-gap-p
#402Epigenetic Bivalency at CDKN2A Locus Distinguishes Senescent from Activated MicrogliaCDKN2A, H3K9me3, DREAM complex (LIN9, LIN37, RBL2)0.630$0.63SDA-2026-04-06-gap-d
#403CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Preventing Template-Dependent MisfoldingCX3CR10.630$0.63SDA-2026-04-04-gap-2
#404Intestinal 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
#405Selective Cholinergic Protection via APP Pathway ModulationAPP0.629$0.66SDA-2026-04-03-gap-a
#406Gut-Brain Axis M-Cell ModulationGP2, SPIB0.629$0.66SDA-2026-04-04-gap-n
#407APOE4-Driven Astrocyte Senescence as Primary TargetAPOE,CDKN1A,BCL2L10.629$0.66SDA-2026-04-04-gap-s
#408TREM2 Antagonism in Late-Stage Tauopathy — Reducing Neuroinflammatory AmplificationTREM20.628$0.61SDA-2026-04-02-gap-0
#409Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's diseaseTREM20.628$0.67SDA-2026-04-04-analy
#410Quantum Coherence Disruption in Cellular CommunicationTUBB30.627$0.69sda-2026-04-01-gap-0
#411Synthetic Biology Approach: Designer Mitochondrial Export SystemsSynthetic fusion proteins0.627$0.67sda-2026-04-01-gap-2
#412Cardiovascular-Neuroinflammatory Dual TargetingTNF/IL60.627$0.66SDA-2026-04-04-gap-2
#413TREM2 Super-Agonist Induction of DAM Program-0.627$0.63SDA-2026-04-16-gap-2
#414Default Mode Network Circuit StabilizationVIP0.627$0.66SDA-2026-04-03-26abc
#415Microbial Metabolite-Mediated α-Synuclein DisaggregationSNCA, HSPA1A, DNMT10.626$0.67SDA-2026-04-01-gap-2
#416Peripheral-to-Central Inflammation Circuit BreakerIL1B0.626$0.67SDA-2026-04-16-gap-b
#417Enteric Nervous System Prion-Like Propagation BlockadeTLR4, SNCA0.625$0.67SDA-2026-04-01-gap-2
#418PINK1/Parkin-Independent Mitophagy Bypass for Enhanced Donor MitochondriaBNIP3/BNIP3L0.624$0.66sda-2026-04-01-gap-2
#419Conditional CRISPR Kill Switches for Aberrant Protein ClearanceUBE3A, PARK2, PINK10.624$0.66SDA-2026-04-03-gap-c
#420Serine/Arginine-Rich Protein Kinase ModulationSRPK10.624$0.67sda-2026-04-01-gap-0
#421Myelin Sulfatide RestorationGAL3ST10.623$0.66SDA-2026-04-03-gap-a
#422Microglial TREM2-Independent Pathway ActivationDAP12, SYK, PLCG20.623$0.66SDA-2026-04-03-gap-d
#423TFEB-PGC1α Mitochondrial-Lysosomal DecouplingTFEB0.622$0.66SDA-2026-04-03-gap-a
#424Cholesterol-CRISPR Convergence Therapy for NeurodegenerationHMGCR, LDLR, APOE regulatory regions0.622$0.65SDA-2026-04-03-gap-c
#425Pharmacological Enhancement of APOE4 GlycosylationST6GAL1, FUT80.622$0.66sda-2026-04-01-gap-0
#426Dual-Phase Medium-Chain Triglyceride InterventionHMGCS2/CPT1A0.622$0.61SDA-2026-04-04-gap-d
#427Microglial ACE Enhancement for Amyloid ClearanceACE0.622$0.65SDA-2026-04-03-gap-a
#428Designer TRAK1-KIF5 fusion proteins accelerate therapeutic mitochondrial deliveryTRAK1_KIF5A0.621$0.66sda-2026-04-01-gap-v
#429CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 DeliveryHDAC3 (class I histone deacetylase)0.620$0.62SDA-2026-04-08-gap-d
#430Microglial Metabolic Trained Immunity via mTOR-HIF1α AxisMTOR/HIF1α0.620$0.62SDA-2026-04-07-gap-d
#431Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 inflammasome activation without impairing normal proteolysisCTSB0.620$0.62SDA-2026-04-04-gap-l
#432TREM2 Agonism to Reprogram Infiltrated Monocytes Toward Neuroprotective PhenotypeTREM20.620$0.61SDA-2026-04-13-gap-d
#433Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic ShiftHIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)0.620$0.62SDA-2026-04-06-gap-p
#434Microglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutamate ToxicitySLC7A110.620$0.60SDA-2026-04-16-gap-f
#435Cross-Cell Type Synaptic Rescue via Tripartite Synapse RestorationSYN1, SLC1A2, and CX3CR10.620$0.65SDA-2026-04-03-gap-s
#436Tau 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
#437C1Q-Induced Foam Cell Formation via Scavenger Receptor UpregulationC1QA/C1QC0.620$0.62SDA-2026-04-07-gap-p
#438Lysosomal pH Restoration Upstream of TFEBATP6V1A0.619$0.65SDA-2026-04-03-gap-d
#439Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1C3/C3aR0.618$0.62SDA-2026-04-07-gap-p
#440Low Complexity Domain Cross-Linking InhibitionTGM20.617$0.66sda-2026-04-01-gap-0
#441LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP1 InductionSPP10.617$0.62SDA-2026-04-06-gap-p
#442Perinatal Immune Challenge PreventionMultiple0.616$0.65SDA-2026-04-04-gap-2
#443Mitochondrial-Cytokine Axis ModulationMitochondrial respiratory complexes and inflammatory cytokine receptors0.616$0.65SDA-2026-04-03-gap-a
#444Spatially-Targeted Regional Vulnerability PreventionRegional vulnerability genes0.616$0.65SDA-2026-04-03-gap-s
#445Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic WindowsTFEB, MAPK14, MAPKAPK2, IL6, CXCL10.614$0.61SDA-2026-04-07-gap-d
#446Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory CascadeAGER0.613$0.65SDA-2026-04-01-gap-2
#447Trinucleotide Repeat Sequestration via CRISPR-Guided RNA TargetingHTT, DMPK, repeat-containing transcripts0.613$0.64SDA-2026-04-03-gap-c
#448Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic EngineeringTDC0.612$0.64SDA-2026-04-01-gap-2
#449Optogenetic Control of Mitochondrial Transfer NetworksChR20.612$0.65sda-2026-04-01-gap-2
#450Complement-Mediated Synaptic Pruning DysregulationC1QA0.612$0.65SDA-2026-04-03-gap-a
#451Test: TREM2 enhances amyloid clearance-0.612$0.61-
#452Synaptic Pruning Precision TherapyC1QA, C3, CX3CR1, CX3CL10.612$0.65SDA-2026-04-04-gap-2
#453HDAC3-Dependent A1 Astrocyte Commitment WindowHDAC30.611$0.61SDA-2026-04-07-gap-d
#454Pharmacogenomic CNS Drug Optimization PlatformCYP450 enzymes, transporters, and drug targets0.611$0.60SDA-2026-04-04-gap-d
#455Epigenetic Memory Reprogramming for Alzheimer's DiseaseBDNF, CREB1, synaptic plasticity genes0.611$0.64SDA-2026-04-03-gap-c
#456APOE4-Lipid Metabolism CorrectionAPOE0.610$0.64SDA-2026-04-04-gap-2
#457H2: Perforant Path Synapse Loss via Early Complement Cascade ActivationC1QA, C1QB, C3, ITGAM0.610$0.61SDA-2026-04-02-gap-e
#458Astrocyte LRP1-mediated tau uptake and APOE4-dependent secretion creates regional susceptibility gradientsLRP10.610$0.61SDA-2026-04-07-gap-d
#459APOE4 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
#460Female 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
#461H1: Senolytic Clearance of Senescent APOE4 AstrocytesCDKN2A (p16Ink4a)0.610$0.61SDA-2026-04-06-gap-d
#462Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB SignalingCREB1, BDNF, NTRK2 (TrkB)0.610$0.61SDA-2026-04-07-gap-p
#463Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease PathologymiR-1550.610$0.61SDA-2026-04-06-gap-p
#464HIF1A stabilization lowers the activation threshold of circadian-disrupted microgliaHIF1A0.609$0.61SDA-2026-04-07-gap-d
#465Microglial priming is primarily epigenetic, with metabolic changes acting as coupled consequences or cofactorsKDM6B0.609$0.61SDA-2026-04-07-gap-d
#466Temporal TFEB Modulation TherapyTFEB0.609$0.65SDA-2026-04-03-gap-d
#467The Glial Ketone Metabolic Shunt HypothesisHMGCS20.608$0.64SDA-2026-04-02-gap-v
#468Correcting Gut Microbial Dopamine Imbalance to Support Systemic Dopaminergic FunctionDDC0.606$0.65SDA-2026-04-01-gap-2
#469Circadian-Gated Ketone Window HypothesisOXCT10.606$0.66SDA-2026-04-03-gap-d
#470Microbiome-Derived Tryptophan Metabolite NeuroprotectionAHR, IL10, TGFB10.605$0.65SDA-2026-04-01-gap-2
#471TREM2-Microglial Clearance Enhancement as Common Mechanism for Injury PreventionTREM20.604$0.59SDA-2026-04-14-gap-p
#472Selective TFEB Cofactor EnhancementTFE30.602$0.64SDA-2026-04-03-gap-d
#473NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for Reverse Senescence-0.602$0.60SDA-2026-04-16-gap-p
#474STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Interruption of IFN-I Feedback LoopingTMEM173 (STING)0.601$0.60SDA-2026-04-15-gap-p
#475TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement CascadeTNF; TNFRSF1A; C1R; C1S0.600$0.60SDA-2026-04-08-gap-p
#476TREM2-Mediated Astroglial Reactivity in NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#477mTORC1 Hyperactivation Impairs Autophagic Flux and Drives SenescenceMTOR/TFEB/TFE30.600$0.60SDA-2026-04-06-gap-p
#478C1Q-Mediated Defective Efferocytosis Driving Necrotic Core ExpansionC1QA/C1QC0.600$0.60SDA-2026-04-07-gap-p
#479APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex NeurodegenerationAPOE40.600$0.60SDA-2026-04-06-gap-p
#480Aberrant Galectin-3 Expression on Stressed Synapses Creates Bridging MoleculesLGALS3 (Galectin-3)0.600$0.60SDA-2026-04-07-gap-p
#481TREM2-Dependent Senescent Microglia Disrupt Astrocyte Communication NetworksTREM2/TYROBP0.600$0.54SDA-2026-04-03-gap-a
#482TREM2-Mediated Oligodendrocyte-Microglia Cross-talk in White Matter NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#483Selective C1q-CRP vs. C1q-IgG Axis InhibitionC1QA/C1QB/C1QC, CRP, FCGR1A0.599$0.61SDA-2026-04-16-gap-p
#484Oligodendrocyte-Targeted Myelin Sulfatide Restoration TherapyCST, GAL3ST10.599$0.63SDA-2026-04-03-gap-d
#485OPC differentiation blockade contributes to white matter degeneration in early-stage ADPDGFRA0.599$0.65SDA-2026-04-04-analy
#486Metabolic Reprogramming via Coordinated Multi-Gene CRISPR CircuitsPGC1A, SIRT1, FOXO3, mitochondrial biogenesis genes0.599$0.63SDA-2026-04-03-gap-c
#487Brain Insulin Resistance with Glucose Transporter DysfunctionGLUT3/GLUT40.596$0.63SDA-2026-04-02-gap-v
#488Multi-Modal CRISPR Platform for Simultaneous Editing and MonitoringDisease-causing mutations with integrated reporters0.596$0.63SDA-2026-04-03-gap-c
#489Programmable Neuronal Circuit Repair via Epigenetic CRISPRNURR1, PITX3, neuronal identity transcription factors0.596$0.63SDA-2026-04-03-gap-c
#490Netrin-1 Gradient RestorationNTN10.595$0.66sda-2026-04-01-gap-0
#491TREM2-mediated microglial tau clearance enhancementTREM20.594$0.84SDA-2026-04-04-gap-t
#492NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement AmplificationNAMPT, SIRT10.592$0.59SDA-2026-04-16-gap-2
#493TREM2 Signaling Bifurcation with Independent TYROBP-Independent Homeostatic MaintenanceTREM20.591$0.60SDA-2026-04-14-gap-p
#494Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A2 PolarizationAHR, CYP1A1, NFKB1, IL60.591$0.60SDA-2026-04-14-gap-p
#495TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse LossTREM2,C1Q0.591$0.63SDA-2026-04-16-gap-p
#496Bacterial Enzyme-Mediated Dopamine Precursor SynthesisTH, AADC0.590$0.66SDA-2026-04-01-gap-2
#497Neuronal MHC Class I Expression as a Selectivity DeterminantH2-Kb (H2-K1), Lilrb4 (LilrB2)0.590$0.59SDA-2026-04-07-gap-p
#498Cardiovascular-Neuroinflammation Crosstalk InterruptionIL1B, TNFA, NLRP30.587$0.62SDA-2026-04-04-gap-2
#499TREM2-Mediated Oligodendrocyte-Microglia Signaling in White Matter NeurodegenerationTREM20.587$0.53SDA-2026-04-03-gap-a
#500Microglia-Derived Extracellular Vesicle Engineering for Targeted Mitochondrial DeliveryRAB27A/LAMP2B0.587$0.63sda-2026-04-01-gap-2
#501TNFRSF25-Mediated Aging Exosome Pathway InhibitionTNFRSF250.587$0.62SDA-2026-04-03-gap-a
#502Senescence-Tau Decoupling TherapyCDKN2A0.585$0.62SDA-2026-04-03-gap-a
#503Mitochondrial-Lysosomal Coupling EnhancerLAMTOR10.585$0.62SDA-2026-04-03-gap-d
#504Gut-Brain Axis Microbiome ModulationGPR43, GPR109A0.585$0.62SDA-2026-04-04-gap-2
#505P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and neurovascular unit dysfunctionP2RY120.585$0.58SDA-2026-04-07-gap-p
#506APOE4 Creates Accelerated, Compressed Reversibility WindowAPOE/TREM2 axis, APOE-TREM2 physical interaction0.584$0.58SDA-2026-04-06-gap-d
#507IGFBPL1-Mediated Homeostatic RestorationIGFBPL10.584$0.62SDA-2026-04-04-gap-2
#508FcRn Transport Bypass StrategyLDLR0.583$0.62SDA-2026-04-12-gap-d
#509Gamma Entrainment Synergy: HBOT-Enhanced Cerebral Perfusion Amplifies SST Interneuron-Targeted Neuromodulation-0.583$0.57SDA-2026-04-16-gap-p
#510ITGAM/CD11b direct binding explains microglial phagocytosis blockadeITGAM0.582$0.58SDA-2026-04-21-gap-d
#511APOE4 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
#512TREM2-Driven Phagocytic Receptor Cascades Determine Mitochondrial Antigen Presentation vs. Intracellular MitophagyTREM20.580$0.58SDA-2026-04-08-gap-p
#513Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement BiosynthesisNFKB1; IKBKB; C1QA; C30.580$0.58SDA-2026-04-08-gap-p
#514AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic NeurodegenerationAQP4; STAT3; MMP90.580$0.58SDA-2026-04-07-gap-p
#515Microglial Replacement and Ontogeny ShiftCCR20.580$0.58SDA-2026-04-07-gap-d
#516Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Through Attenuated ChemotaxisP2RY120.580$0.58SDA-2026-04-06-gap-p
#517Astrocyte cGAS/STING Activation Converts Protective into Destructive NeuroinflammationSTING (TMEM173) in astrocytes (GFAP+ cells)0.580$0.58SDA-2026-04-07-gap-p
#518H7: Dual-Target Strategy (Senolytics + APOE4→3 Conversion)APOE; CDKN2A0.580$0.58SDA-2026-04-06-gap-d
#519H5: Complement Dysregulation Drives Synapse Loss via Senescent APOE4 AstrocytesC3; C3AR1; C5AR10.580$0.58SDA-2026-04-06-gap-d
#520TREM2 Promoter Silencing via DNA HypermethylationTREM20.580$0.58SDA-2026-04-07-gap-d
#521LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and downstream NLRP3 activationLAMP2 (LGMN)0.580$0.58SDA-2026-04-04-gap-l
#522Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 SignalingNLRP3, LRP1, IL1B, TNF0.580$0.58SDA-2026-04-07-gap-p
#523αvβ3 Integrin-FAK-SYK-CARD9/NF-κB PathwayITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD90.580$0.58SDA-2026-04-06-gap-p
#524Complement-Mediated Synaptic ProtectionC1QA0.580$0.62SDA-2026-04-04-gap-2
#525IGFBPL1-Mediated Microglial ReprogrammingIGFBPL10.579$0.62SDA-2026-04-04-gap-2
#526TREM2-Astrocyte Communication in Microglial DysfunctionTREM20.579$0.00SDA-2026-04-03-gap-a
#527Spatial Transcriptome-Guided Precision Cell TherapySOX10 and DLX1/20.578$0.62SDA-2026-04-03-gap-s
#528Dynamic Microglial Phenotype Switching Biomarker Panel for Neuroinflammatory Treatment StratificationTREM20.577$0.58SDA-2026-04-16-gap-p
#529LRP1-Dependent Tau Uptake DisruptionLRP10.576$0.79SDA-2026-04-04-gap-t
#530Oligodendrocyte Progenitor Cell Metabolic ReprogrammingPDK1, PFKFB3, LDHA0.575$0.61SDA-2026-04-03-gap-d
#531TREM2-Senescence Cascade in Astrocyte-Microglia Communication BreakdownTREM20.574$0.00SDA-2026-04-03-gap-a
#532TREM2-P2RY12 Balance Restoration TherapyTREM20.571$0.61SDA-2026-04-04-gap-2
#533Disease-Associated Microglia (DAM) Program Drives IBA1 DownregulationTREM2/TYROBP0.571$0.57SDA-2026-04-07-gap-p
#534PINK1/PARK2-Mediated Mitophagy Enhancement for Neuroinflammation ControlPINK10.571$0.57SDA-2026-04-03-gap-i
#535Neuronal Subtype-Specific Alpha-Synuclein Expression NormalizationSNCA0.571$0.60SDA-2026-04-03-gap-d
#536VCP-Mediated Autophagy EnhancementVCP0.571$0.76SDA-2026-04-04-gap-t
#537Blocking Astrocyte-Mediated Tau Re-Spreading via Cx43 Hemichannel InhibitionGJA1 (Connexin-43)0.570$0.57SDA-2026-04-04-gap-t
#538CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estrogen Receptor-alpha Suppression of NLRP3ESR10.570$0.57SDA-2026-04-06-gap-p
#539Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 InhibitionHDAC6 (class IIb histone deacetylase)0.570$0.57SDA-2026-04-08-gap-d
#540Direct NF-κB Transcriptional Regulation of C1q Genes in MicrogliaRELA; C1QA/C1QB/C1QC0.570$0.57SDA-2026-04-08-gap-p
#541Tau-Independent Microtubule Stabilization via MAP6 EnhancementMAP60.567$0.73sda-2026-04-01-gap-0
#542Temporal Gating of Microglial ResponsesCLOCK, ARNTL0.565$0.63SDA-2026-04-04-gap-2
#543Closed-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
#544Closed-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
#545Closed-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
#546Timed 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
#547Fractalkine Axis Amplification via CX3CR1 Positive Allosteric ModulatorsCX3CR10.563$0.69sda-2026-04-01-gap-v
#548HCN1-Mediated Resonance Frequency Stabilization TherapyHCN10.562$0.73sda-2026-04-01-gap-0
#549Temporal cGAS-STING Activation Stage-Specific Therapeutic TargetingSTING (TMEM173)0.560$0.56SDA-2026-04-07-gap-p
#550Persistent 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
#551Complement C1q Suppression as Mechanism Linking Exercise Plasma to PV Interneuron ProtectionC1QA0.560$0.55SDA-2026-04-14-gap-p
#552MOG-IgG induces spinal cord demyelination through Fcγ receptor-dependent macrophage activationMOG, FCGR1A, FCGR3A, FCGR2A, SYK, IRAK40.560$0.56SDA-2026-04-08-gap-p
#553AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metabolic Coupling DisruptionAQP4; SLC16A1 (MCT1); SLC16A3 (MCT4)0.560$0.56SDA-2026-04-07-gap-p
#554P2X7R PET Imaging for NLRP3 Inflammasome-Associated PrimingP2RX7/NLRP30.560$0.56SDA-2026-04-06-gap-d
#555Extracellular Vesicle Biogenesis ModulationCHMP4B0.558$0.68SDA-2026-04-04-gap-t
#556Circadian-Gated Maresin Biosynthesis AmplificationALOX120.557$0.74sda-2026-04-01-gap-0
#557Test: TREM2 enhances amyloid clearance-0.555$0.55-
#558Ketone-Primed Thalamocortical Enhancement of Glymphatic Tau ClearanceGRIN2B0.555$0.56SDA-2026-04-03-26abc
#559GluN2B-Mediated Microglial Activation and Tau PropagationGRIN2B0.555$0.56SDA-2026-04-03-26abc
#560Inhibitory Neuron-Selective WNT Signaling RestorationWNT3A, CTNNB1, TCF7L20.554$0.62SDA-2026-04-03-gap-d
#561Synaptic Vesicle Tau Capture InhibitionSNAP250.554$0.69SDA-2026-04-04-gap-t
#562Profilin-1 Cytoskeletal Checkpoint EnhancementPFN10.554$0.60SDA-2026-04-03-gap-a
#563Dual NF-κB/MMP Inhibition StrategyNFKB10.554$0.57SDA-2026-04-16-gap-b
#564Closed-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
#565HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.551$0.80SDA-2026-04-04-gap-t
#566Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation WindowsNLRP30.551$0.55SDA-2026-04-15-gap-p
#567Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional ControlSPP10.551$0.55SDA-2026-04-15-gap-p
#568H2: SASP Neutralization via JAK/STAT Inhibition Preserves Astrocyte FunctionIL6R; JAK1; STAT30.550$0.55SDA-2026-04-06-gap-d
#569Digital Twin-Guided Metabolic ReprogrammingPPARGC1A/PRKAA10.550$0.70sda-2026-04-01-gap-0
#570C1q Binding to Specific Synaptic Proteomes via Neurexin/Neuroligin ComplexesNRXN1, NLGN1 (Neuroligin 1)0.550$0.55SDA-2026-04-07-gap-p
#571Oligodendrocyte DNA Repair EnhancementPARP10.550$0.59SDA-2026-04-03-gap-s
#572Surface Exposure of SENP1-β1 Integrin Complex Enables Targeted Senolytic EliminationSENP1, ITGB1 (β1 integrin), ITGAM (CD11b)0.550$0.55SDA-2026-04-06-gap-d
#573Combined NAMPT-Alectinib Targeting of SASP-Complement CascadeNAMPT, SIRT1, C1QA/C1QB/C1QC, IL1B0.549$0.55SDA-2026-04-16-gap-p
#574YWHAG-Mediated TFEB Subcellular TargetingYWHAG0.549$0.62SDA-2026-04-03-gap-d
#575Perinatal Hypoxia-Primed Microglia TargetingHIF1A, NFKB10.548$0.59SDA-2026-04-04-gap-2
#576SYK-Independent TREM2 Pathways Remain Functional in TYROBP DeficiencySYK, TREM20.548$0.54SDA-2026-04-14-gap-p
#577CD300f Immune Checkpoint ActivationCD300F0.545$0.61SDA-2026-04-03-gap-a
#578Trans-Synaptic Adhesion Molecule ModulationNLGN10.544$0.63SDA-2026-04-04-gap-t
#579Temporal Decoupling via Circadian Clock ResetCLOCK0.543$0.77sda-2026-04-01-gap-0
#580TREM2-GluN2B Circuit: Microglial Control of Thalamocortical Oscillations and Glymphatic Tau ClearanceTREM20.543$0.00SDA-2026-04-03-26abc
#581P2Y6R 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
#582Systemic IL-6–STAT3–Hepatic C3 Axis and BBB-Mediated Complement TranslocationIL6; STAT3; C30.540$0.54SDA-2026-04-08-gap-p
#583H6: Epigenetic Reset via APOE4→APOE3 Conversion Reverses SenescenceAPOE; HDAC1; EZH20.540$0.54SDA-2026-04-06-gap-d
#584H5: Olfactory System as a Toxicant Funnel into Layer IINLRP3, CX3CR1, TLR40.540$0.54SDA-2026-04-02-gap-e
#585Soluble 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
#586TAM Receptor (MERTK/AXL) Cross-RegulationMERTK, AXL, TYRO3, PROS1 (Protein S), GAS60.540$0.54SDA-2026-04-06-gap-p
#587Lysosomal Membrane Repair EnhancementCHMP2B0.538$0.72sda-2026-04-01-gap-0
#588ABCA7-TREM2 Co-Targeting for Microglial Lipid HandlingABCA7 + TREM2 (combinatorial)0.538$0.54SDA-2026-04-14-gap-p
#589Glymphatic System-Enhanced Antibody Clearance ReversalAQP40.537$0.71sda-2026-04-01-gap-0
#590Test: TREM2 enhances amyloid clearance-0.537$0.54-
#591Cerebrospinal 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
#592CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering NF-κB-Dependent SPP1 TranscriptionSPP10.535$0.74SDA-2026-04-06-gap-p
#593NFκB/C1Q SASP Modulation for Synaptic Protection-0.534$0.53SDA-2026-04-16-gap-p
#594TREM2-Mediated Microglial Checkpoint TherapyTREM20.534$0.58SDA-2026-04-03-gap-s
#595Blood-Brain Barrier SPM Shuttle SystemTFRC0.533$0.76sda-2026-04-01-gap-0
#596Cryptic Exon Silencing RestorationTARDBP0.531$0.73sda-2026-04-01-gap-v
#597NLRP3 Inflammasome Chromatin Priming Through H3K27ac AccumulationNLRP30.530$0.53SDA-2026-04-07-gap-d
#598TSPO PET Kinetic Modeling for Priming State DiscriminationTSPO0.530$0.53SDA-2026-04-06-gap-d
#599Therapeutic Repurposing: C1-INH as Plaque-Stabilizing AgentC1R/C1S0.530$0.53SDA-2026-04-07-gap-p
#600C1Q-Angiogenic Axis Promoting Plaque NeovascularizationC1QA/C1QC0.530$0.53SDA-2026-04-07-gap-p
#601Modulating Tunneling Nanotube (TNT) Formation via M-Sec/Noradrenaline SignalingTNFRSF12A (M-Sec)0.530$0.53SDA-2026-04-04-gap-t
#602CX3CR1-Targeted AntimiR-155 Oligonucleotides for Microglial Priming ReversalMIR155 (microRNA-155)0.530$0.53SDA-2026-04-08-gap-d
#603Astrocytic Lactate Shuttle Enhancement for Grid Cell BioenergeticsSLC16A20.529$0.69sda-2026-04-01-gap-0
#604TREM2 Epigenetic Window for Microglial Lipid MetabolismTREM2/HDAC10.525$0.53SDA-2026-04-07-gap-d
#605Circadian Clock Epigenetic Desynchronization WindowBMAL1/HDAC30.524$0.52SDA-2026-04-07-gap-d
#606TREM2-Dependent Microglial Control of Thalamocortical-Glymphatic Tau ClearanceTREM20.524$0.00SDA-2026-04-03-26abc
#607TREM2 Agonism to Redirect Microglia from Synaptic Pruning to OPTN-Deficient Neuron ProtectionTREM20.521$0.51SDA-2026-04-14-gap-p
#608Restoring AQP4 Astrocyte Polarization Enhances Glymphatic Tau Clearance and Limits Template-Dependent SpreadingAQP40.520$0.52SDA-2026-04-04-gap-2
#609Mitochondrial DNA Damage and cGAS-STING Activation Induces Microglial SenescenceCGAS/STING1/TMEM1730.520$0.52SDA-2026-04-06-gap-p
#610Blood Monocyte Epigenetic Signature as Surrogate for Microglial PrimingEpigenetic landscape (TLR4, NLRP3, IL1B regulatory regions)0.520$0.52SDA-2026-04-06-gap-d
#611Loss of Nuclear Lamin B1 Distinguishes Senescent Microglia from Inflammatory ActivationLMNB1 (Lamin B1)0.520$0.52SDA-2026-04-06-gap-d
#612Epigenetic Dysregulation of APOE Microglial ExpressionAPOE0.520$0.52SDA-2026-04-07-gap-d
#613Severely Depleted mtDNA and Impaired OXPHOS Defines Senescent MicrogliaMT-ND1, MT-CO1, TFAM, SIRT30.520$0.52SDA-2026-04-06-gap-d
#614Lipid Nanoparticle Encapsulation of IGFBPL1-mRNAIGFBPL10.520$0.52SDA-2026-04-06-gap-d
#615Dysregulated 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
#616Telomere Attrition and DNA Damage Response Activation Induces Microglial SenescenceTP53/CDKN2A/CDKN1A/ATM/ATR0.520$0.52SDA-2026-04-06-gap-p
#617M-Sec/TNTA2-mediated tunneling nanotube formation drives glia-neuron tau propagation in mid-stagesTNFAIP20.520$0.52SDA-2026-04-07-gap-d
#618GATA4 Stabilization and NF-κB Co-activation Identifies Senescent MicrogliaGATA4, SQSTM1/p62, NFKB subunits0.520$0.52SDA-2026-04-06-gap-d
#619Piezoelectric Nanochannel BBB DisruptionCLDN5, OCLN0.519$0.70sda-2026-04-01-gap-0
#620NRF2 Activation to Counteract Oxidative Stress from RGS6 Deficiency-0.518$0.52SDA-2026-04-17-gap-p
#621Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late InhibitionSPP10.518$0.52SDA-2026-04-07-gap-p
#622Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Downregulation via NRF2NRF2/NFE2L20.517$0.52SDA-2026-04-07-gap-p
#623Hippocampus ages transcriptionally faster than cerebellum, defining a regional vulnerability axis conserved across speciesCLU0.516$0.50aging-mouse-brain-20
#624Vocal Cord Neuroplasticity StimulationCHR2/BDNF0.515$0.67sda-2026-04-01-gap-0
#625GAS6/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
#626Test: TREM2 enhances amyloid clearance-0.512$0.51-
#627Primed microglia occupy a hybrid high-glycolysis and high-respiration metabolic statePDHA10.510$0.51SDA-2026-04-07-gap-d
#628Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated FailureC1Q0.510$0.51SDA-2026-04-02-gap-s
#629Circulating IBA1 Protein Absorption/Interference with DetectionAIF1/IBA10.507$0.51SDA-2026-04-07-gap-p
#630PKM2 nuclear translocation bridges metabolism and inflammatory transcription in primed microgliaPKM20.506$0.51SDA-2026-04-07-gap-d
#631TYRO3-STAT1 Axis to Preserve Parvalbumin Interneuron Function by Suppressing IL-1β-Mediated Inflammatory DamageTYRO30.506$0.52SDA-2026-04-14-gap-p
#632NETosis Amplification by C1Q in Plaque NeutrophilsC1QA/C1QC0.500$0.50SDA-2026-04-07-gap-p
#633Selectively Inhibit Maladaptive AQP4-Driven Astrocyte-Microglia Inflammatory Signaling in Parkinsonian InjuryAQP4, NFKB1, IL1B, TNF0.500$0.50SDA-2026-04-07-gap-p
#634APOE4 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
#635Early Postnatal TGF-beta Signaling Establishes Lifelong Regional Vulnerability Through Irreversible Transcriptional ImprintingTGFBR10.500$0.50SDA-2026-04-06-gap-p
#636CX3CR1 PET with Nano-bodies for Microglial Surveillance State MappingCX3CR10.500$0.50SDA-2026-04-06-gap-d
#637Alectinib-C1q Complex Hijacks TREM2's Synaptic Protective Binding InterfaceC1QA/C1QB/C1QC, TREM20.500$0.52SDA-2026-04-16-gap-p
#638TREM2-Mediated Microglial Dysfunction Drives Tau-Induced Blood-Brain Barrier BreakdownTREM20.499$0.00SDA-2026-04-03-26abc
#639SIRT1-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
#640Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critical Neuroinflammatory WindowsNLRP30.496$0.00SDA-2026-04-15-gap-p
#641TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated Survival and Metabolic SignalingSPP10.496$0.50SDA-2026-04-06-gap-p
#642TREM2-Mediated Microglial Metabolic Reprogramming Accelerates Tau Pathological SpreadTREM20.494$0.00SDA-2026-04-03-26abc
#643YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Perivascular FibroblastsSPP10.492$0.70SDA-2026-04-06-gap-p
#644GluN2B-Regulated Microglial Phagocytosis of Tau Aggregates via CX3CR1 SignalingGRIN2B0.491$0.00SDA-2026-04-03-26abc
#645P2RY12/P2RY13 Purinergic Receptor Metabolic RewiringP2RY12, P2RY13, CTNNB1 (β-catenin), GSK3β0.490$0.49SDA-2026-04-06-gap-p
#646Testosterone-Derived DHT Amplifies Microglial Androgen Receptor Signaling Driving Male-Biased NeuroinflammationAR0.490$0.49SDA-2026-04-06-gap-p
#647Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal ExpressionMFGE8, NPTX2 (Neuronal Pentraxin 1)0.490$0.49SDA-2026-04-07-gap-p
#648C1q-Mediated Delivery of miR-33 Antisense Oligonucleotides for Enhanced APOE4 LipidationmiR-33a/miR-33b0.489$0.49SDA-2026-04-16-gap-d
#649APOE4 Structural Remodeling via HSP70 Chaperone Enhancement StrategyHSP70/APOE40.486$0.00SDA-2026-04-16-gap-d
#650TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inflammasome RegulationTFEB0.485$0.00SDA-2026-04-03-gap-i
#651PINK1/PARK2-LC3 Mitophagy EnhancementPINK10.485$0.48SDA-2026-04-03-gap-i
#652GluN2B-Mediated Perivascular Pericyte Control of Glymphatic Tau ClearanceGRIN2B0.485$0.00SDA-2026-04-03-26abc
#653SIRT3 gates microglial surveillance versus primed metabolism through mitochondrial deacetylationSIRT30.482$0.48SDA-2026-04-07-gap-d
#654ISG Threshold Model Explains Acute vs Chronic Neurodegeneration OutcomesUSP18 / JAK/STAT pathway0.480$0.48SDA-2026-04-07-gap-p
#655Ferroptosis as Context-Dependent and Motor Neuron-Subtype Selective-0.475$0.53SDA-2026-04-18-gap-d
#656Intranasal IGFBPL1 Delivery via Olfactory PathwayIGFBPL10.470$0.47SDA-2026-04-06-gap-d
#657CD44-Mediated Src/PI3K/Akt Signaling CascadeCD44, SRC, PI3K p85 (PIK3R1), MTOR0.470$0.47SDA-2026-04-06-gap-p
#658C1Q-Glia Cross-Talk in Vascular Dementia PathogenesisC1QA/C1QC0.470$0.47SDA-2026-04-07-gap-p
#659APOE and TREM2 interact to modulate age-dependent microglial dysfunctionTREM20.467$0.50aging-mouse-brain-20
#660Source-Specific SPP1 Inhibition: Perivascular Cell TargetingSPP1 (perivascular)0.466$0.47SDA-2026-04-07-gap-p
#661Cross-Tissue Communication DisruptionMULTIPLE0.466$0.51SDA-2026-04-16-gap-b
#662Microglial Priming Window for HDAC1-Dependent DAM TransitionHDAC10.463$0.46SDA-2026-04-07-gap-d
#663TYROBP Network Hyperactivation Marks Point of No ReturnTYROBP/SYK axis, MAPK/ERK signaling0.463$0.46SDA-2026-04-06-gap-d
#664CSF 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
#665TSPO-Mediated TDP-43 Mitochondrial ImportTSPO (TSPO), TDP-43-TSPO protein-protein interaction0.460$0.46SDA-2026-04-07-gap-p
#666CSF 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
#667Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology into NeuroinflammationMLKL / RIPK10.460$0.46SDA-2026-04-07-gap-p
#668Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional ControlSPP10.459$0.00SDA-2026-04-15-gap-p
#669Selective Microglial Senescence Targeting via TREM2 ModulationTREM20.459$0.50SDA-2026-04-04-gap-s
#670Kinase Inhibitor-C1q Structural Convergence for Bifunctional Drug DesignC1QA/C1QB/C1QC, ALK, SYK0.458$0.50SDA-2026-04-16-gap-p
#671C1q Inhibition Prevents Synaptic Mitochondrial Dysfunction via Microglial-Neuronal Cross-Talk NormalizationC1QA/C1QB/C1QC0.455$0.45SDA-2026-04-15-gap-p
#672C1q-Alectinib Complexation Disrupts Tight Junction Integrity to Enable Paracellular Brain PenetrationCLDN5, OCLN0.455$0.46SDA-2026-04-17-gap-d
#673Mitochondrial Damage-Triggered SPP1 Inflammasome CouplingSPP10.453$0.00SDA-2026-04-15-gap-p
#674TREM2-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
#675α4β1 Integrin (VLA-4) and JAK/STAT PathwayITGA4, ITGB1 (α4β1 heterodimer), JAK1/JAK2, STAT30.450$0.45SDA-2026-04-06-gap-p
#676Paraneoplastic 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
#677Astrocytic APOE4 Disruption of GABAergic Support Increasing Neuronal VulnerabilitySLC1A2 (GLT-1), GABRA1, GABRB3, GAD10.450$0.45SDA-2026-04-07-gap-p
#678Monocyte Trojan Horse Cell TherapyIGFBPL10.450$0.45SDA-2026-04-06-gap-d
#679Astrocytic SPP1 Modulation for Neuroinflammatory ResolutionSPP10.447$0.00SDA-2026-04-15-gap-p
#680MITF 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
#681Microglial Membrane Camouflage Exploits CD47-SIRPα Checkpoint DisinhibitionCD47, SIRPA, PTPN6, PTPN110.444$0.46SDA-2026-04-16-gap-p
#682RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular FibroblastsSPP10.442$0.44SDA-2026-04-06-gap-p
#683Test: TREM2 enhances amyloid clearance-0.437$0.44-
#684Blood-Brain Barrier Disruption Enabling Peripheral Inflammatory InsultPDGFRB, CLDN5, OCLN, FGB0.430$0.43SDA-2026-04-07-gap-p
#685GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation-0.429$0.43SDA-2026-04-17-gap-p
#686Lactate-HCAR1 signaling maintains a self-reinforcing glycolytic priming loopHCAR10.427$0.43SDA-2026-04-07-gap-d
#687C1q-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
#688C1q-Conjugated miR-33 ASO Brain Delivery for Enhanced APOE4 LipidationmiR-33a/miR-33b0.423$0.00SDA-2026-04-16-gap-d
#689P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription via Calcineurin/NFAT PathwaySPP10.423$0.63SDA-2026-04-06-gap-p
#690IGFBPL1 Peptide Mimetics for Drug-Like BBB PermeabilityIGFBPL10.420$0.66SDA-2026-04-06-gap-d
#691LncRNA-HDAC1 Complex Formation Locks Microglia in Primed StateHDAC1/NEAT10.420$0.45SDA-2026-04-07-gap-d
#692Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic VulnerabilityC1QA, C3, C3AR1 (complement cascade)0.419$0.39SDA-2026-04-13-gap-p
#693P2RY12-mediated cerebral VSMC dysfunction establishes a vicious cycle with microglial P2RY12 activationP2RY12 (dual: VSMC + microglia)0.418$0.42SDA-2026-04-07-gap-p
#694C1q-Alectinib Complexation Enhances CNS Penetration via Microglial C1qR-Mediated Uptake and RedistributionC1QBP0.415$0.47SDA-2026-04-17-gap-d
#695HDAC2-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
#696Test: TREM2 enhances amyloid clearance-0.405$0.41-
#697Test: TREM2 enhances amyloid clearance-0.400$0.41-
#698Test: TREM2 enhances amyloid clearance-0.400$0.41-
#699Test: TREM2 enhances amyloid clearance-0.400$0.41-
#700Test: TREM2 enhances amyloid clearance-0.400$0.41-
#701Test: TREM2 enhances amyloid clearance-0.400$0.40-
#702CSF1R Inhibition Reversal Window Depends on Microglia Replacement KineticsCSF1R, nestin+ progenitor pool0.395$0.40SDA-2026-04-06-gap-d
#703BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic primingARNTL0.389$0.39SDA-2026-04-07-gap-d
#704LRP1-Autophagy BBB Permeabilization for Antibody TransportLRP1; ATG7; OPTN (autophagy pathway); CLDN5 (tight junctions)0.380$0.38SDA-2026-04-02-gap-b
#705Partial Agonist/SPP1 Splice Variant Strategy: Splice-Switching TherapeuticsSPP1 splicing factors0.375$0.41SDA-2026-04-07-gap-p
#706P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via SASP secretionP2RY120.373$0.37SDA-2026-04-07-gap-p
#707Ferroptosis as Epiphenomenon of Terminal Collapse-0.363$0.43SDA-2026-04-18-gap-d
#708Age-related neuroinflammation mimics early Alzheimer's disease pathologyGFAP0.362$0.50aging-mouse-brain-20
#709Ferroptosis as Primary Driver of Motor Neuron Death-0.339$0.40SDA-2026-04-18-gap-d
#710Novel Hypothesis on Metabolic Dysregulation in NeurodegenerationSLC16A1 (MCT1)0.330$0.39-
#711CHMP2B vs. CHMP2A Subunit Targeting Creates a Therapeutic Window in ESCRT-Dependent Tau SortingCHMP2B, CHMP2A, CHMP4B0.330$0.33SDA-2026-04-06-gap-d
#712[Archived Hypothesis]-0.300$0.30-
#713[Archived Hypothesis]-0.300$0.30-
#714C1q-Alectinib Complexation Facilitates Brain Penetration via Receptor-Mediated Transcytosis-0.145$0.21SDA-2026-04-17-gap-d
#715Direct C1q Binding Enables FcγR-Independent Complement Activation on Tumor Cells-0.138$0.21SDA-2026-04-17-gap-d
#716Human Serum Albumin-Mediated Displacement Creates False-Positive C1q Binding Signals-0.136$0.20SDA-2026-04-17-gap-d
#717C1q Binding Reflects Broader Kinase Inhibitor Promiscuity Rather Than Specific Complement Targeting-0.124$0.19SDA-2026-04-17-gap-d
#718Alectinib Binds Mitochondrial C1q-like Proteins (C1QDC1) Rather Than Circulating C1q-0.122$0.18SDA-2026-04-17-gap-d
#719C1q Binding Analysis Across ALK Inhibitor Chemical Series Would Resolve Specificity-0.115$0.17SDA-2026-04-17-gap-d
#720NLRP3 Inflammasome Suppression via Selective Caspase-1 Inhibition-0.105$0.16SDA-NEUROINFLAM-BIOM
#721TYROBP Causal Network Inhibition for Microglial Repolarization-0.105$0.20SDA-NEUROINFLAM-BIOM
#722CD300f Immunoglobulin Receptor as Neuroinflammatory Brake-0.105$0.21SDA-NEUROINFLAM-BIOM
#723TREM2 Agonism with CX3CR1 Antagonism for Microglial Homeostasis-0.105$0.17SDA-NEUROINFLAM-BIOM
#724P2RX7-PANX1 Channel Blockade for Neuroinflammatory Cascade Interruption-0.105$0.20SDA-NEUROINFLAM-BIOM
#725IL-33/ST2 Axis Augmentation for Synaptic Protection-0.105$0.20SDA-NEUROINFLAM-BIOM
#726Alectinib'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