🔬 Microglial Biology

Immune cell activation, TREM2 signaling, and neuroinflammation

Index Score
0.000
Hypotheses
380
Unique Genes
228
Avg Score
0.631

Portfolio Strategy

This mission tracks 380 hypotheses targeting 228 unique genes. The portfolio index of 0.000 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 (380)

#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
#5Closed-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
#6PLCG2 Allosteric Modulation as a Precision Therapeutic for TREM2-Dependent Microglial DysfunctionPLCG20.941$0.82SDA-2026-04-01-gap-0
#7Closed-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
#8CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microglial Senescence ReversalCYP46A10.921$0.80SDA-2026-04-01-gap-l
#9Autophagy-Senescence Axis Therapeutic WindowATG7,BCL2,BCL2L10.921$0.93SDA-2026-04-04-gap-s
#10HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM TransitionHK20.919$0.91SDA-2026-04-16-gap-d
#11Palmitoylethanolamide-Based Endocannabinoid TherapyPPARA0.919$0.80SDA-2026-04-16-gap-b
#12TREM2-ASM Crosstalk in Microglial Lysosomal SenescenceSMPD10.910$0.79SDA-2026-04-03-gap-a
#13TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.907$0.81SDA-2026-04-03-gap-a
#14Closed-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
#15CSF1R Inhibition-Mediated Microglial Replacement as a State Transition ResetCSF1R0.898$0.85SDA-2026-04-16-gap-d
#16Closed-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
#17SIRT1-Mediated Reversal of TREM2-Dependent Microglial SenescenceSIRT10.895$0.83SDA-2026-04-03-gap-a
#18TREM2-Mediated Astrocyte-Microglia Crosstalk in NeurodegenerationTREM20.892$0.77SDA-2026-04-03-gap-a
#19Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.888$0.91SDA-2026-04-01-gap-2
#20Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially IrreversibleAPP/PSEN1 (Aβ production), CHAT (cholinergic synthesis)0.887$0.81SDA-2026-04-12-20260
#21TREM2-APOE Axis Dissociation for Selective DAM ActivationTREM2-APOE axis0.886$0.86SDA-2026-04-01-gap-0
#22TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.880$0.92SDA-2026-04-03-gap-a
#23Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State Transition RestorationIFNG0.879$0.87SDA-2026-04-16-gap-d
#24TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.875$0.92SDA-2026-04-03-gap-a
#25TREM2-Mediated Cholesterol Dysregulation in Microglial SenescenceCYP46A10.869$0.89SDA-2026-04-03-gap-a
#26Complement Cascade Inhibition Synaptic Protection-0.867$0.81SDA-2026-04-16-gap-p
#27Closed-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
#28Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilizationBDNF0.861$0.81SDA-2026-04-03-26abc
#29Closed-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
#30TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM TransitionNAMPT0.858$0.74SDA-2026-04-16-gap-d
#31Senescent Cell ASM-Complement Cascade InterventionSMPD10.852$0.87SDA-2026-04-01-gap-l
#32Microglial Senescence Prevention via TREM2/SASP Axis-0.847$0.78SDA-2026-04-16-gap-p
#33TYROBP (DAP12) Conditional Antagonism for Early-Stage NeuroprotectionTYROBP0.844$0.72SDA-2026-04-01-gap-0
#34miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglial State TransitionMIR1550.843$0.82SDA-2026-04-16-gap-d
#35Gamma Oscillation Enhancement Synergy-0.838$0.82SDA-2026-04-16-gap-p
#36Sequential 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
#37Closed-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
#38Closed-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
#39Real-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
#40Microglial 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
#41Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.822$0.72SDA-2026-04-01-gap-2
#42Ketone Utilization Index as Metabolic Flexibility BiomarkerHMGCS20.819$0.83SDA-2026-04-04-gap-d
#43Extracellular Vesicle Biogenesis ModulationCHMP4B0.814$0.73SDA-2026-04-04-gap-t
#44TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau ClearanceTREM20.812$0.86SDA-2026-04-03-26abc
#45CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerability ThresholdsAPOE, CLU0.811$0.69SDA-2026-04-15-gap-d
#46LRP1-Dependent Tau Uptake DisruptionLRP10.808$0.77SDA-2026-04-04-gap-t
#47CSF1R-TREM2 Co-Agonism for Sustained Microglial ExpansionCSF1R-TREM20.808$0.78SDA-2026-04-01-gap-0
#48P2RX7-Mediated Exosome Secretion BlockadeP2RX70.807$0.78SDA-2026-04-04-gap-t
#49Neutrophil Extracellular Trap (NET) InhibitionPADI40.806$0.74SDA-2026-04-16-gap-b
#50Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.805$0.78SDA-2026-04-01-gap-2
#51Calcium-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
#52TREM2-mTOR Co-Agonism for Metabolic ReprogrammingTREM2-mTOR pathway0.803$0.74SDA-2026-04-01-gap-0
#53Dual-Receptor Antibody Shuttling-0.803$0.87-
#54Prime Editing Precision Correction of APOE4 to APOE3 in MicrogliaAPOE0.803$0.68SDA-2026-04-03-gap-c
#55Targeting 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
#56Mitochondrial DNA-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.803$0.68SDA-2026-04-01-gap-2
#5740 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated MicrogliaACSL40.801$0.76SDA-2026-04-03-gap-s
#58TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism DysregulationTREM2/TYROBP0.800$0.72SDA-2026-04-06-gap-p
#59Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective EffectorMANF, CDNF0.798$0.73SDA-2026-04-16-gap-p
#60Microglial TREM2-SYK Pathway EnhancementTREM20.798$0.74SDA-2026-04-03-gap-s
#61SASP-Driven Microglial Metabolic Reprogramming in Synaptic PhagocytosisHK2/PFKFB30.796$0.94sda-2026-04-01-gap-0
#62Microglial-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.792$0.82SDA-2026-04-03-26abc
#63Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid PathologyCHRNA7 (α7 nicotinic receptor), BACE10.785$0.81SDA-2026-04-12-20260
#64Closed-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
#65TREM2-mediated microglial tau clearance enhancementTREM20.780$0.67SDA-2026-04-04-gap-t
#66LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine in Disease-Associated MicrogliaLPCAT30.779$0.82SDA-2026-04-03-gap-s
#67ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter Degeneration in Alzheimer's DiseaseACSL40.779$0.82SDA-2026-04-03-gap-s
#68ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE PeroxidationALOX150.777$0.82SDA-2026-04-03-gap-s
#69CX3CR1-TREM2 Integration for Synapse Pruning NormalizationCX3CR1-TREM20.776$0.76SDA-2026-04-01-gap-0
#70LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Disease-Associated MicrogliaLPCAT30.776$0.67SDA-2026-04-03-gap-s
#71Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory PathwayGPNMB, CD440.772$0.71SDA-2026-04-16-gap-p
#72LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Disease-Associated MicrogliaLPCAT30.770$0.66SDA-2026-04-03-gap-s
#73Oligodendrocyte Precursor Cell Senescence in White Matter DiseaseCSPG4,OLIG2,BCL20.769$0.73SDA-2026-04-04-gap-s
#74Lysosomal Cathepsin-Dependent Tau Clearance-0.767$0.75SDA-2026-04-16-gap-p
#75cGAS-STING Pathway Hyperactivation Mediates Tau PropagationcGAS (CGAS), STING (TMEM173)0.760$0.76SDA-2026-04-02-gap-2
#76INPP5D (SHIP1) Inhibition to Shift Microglial PolarizationINPP5D0.758$0.74SDA-2026-04-01-gap-0
#77sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy-0.757$0.87SDA-2026-04-16-gap-p
#78Test: TREM2 enhances amyloid clearance-0.755$0.70-
#79Dual-Circuit Tau Vulnerability CascadeMAPT0.754$0.70SDA-2026-04-03-26abc
#80Enhancing Microglial Phagocytosis of Extracellular Tau via TREM2 ActivationTREM20.750$0.75SDA-2026-04-04-gap-t
#81TREM2-CSF1R Cross-Talk in Microglial Metabolic ReprogrammingTREM2, CSF1R0.748$0.90SDA-2026-04-03-gap-a
#82C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV Interneuron Input Elimination in Alzheimer's DiseaseC1QA, C1QB0.747$0.70SDA-2026-04-15-gap-d
#83TREM2-SIRT1 Metabolic Senescence Circuit in Microglial AgingTREM20.744$0.90SDA-2026-04-03-gap-a
#84miR-33 Antisense Oligonucleotide Hyper-Lipidation StrategymiR-33/ABCA10.741$0.69SDA-2026-04-16-gap-d
#85TREM2-APOE4 Co-targeting — Simultaneous Correction of Lipid Sensing and Clearance DeficitsTREM2, APOE0.741$0.62SDA-2026-04-02-gap-0
#86Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor ImpairmentMAPT0.737$0.76SDA-2026-04-03-26abc
#87Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Antagonist in Tau PhaseTREM2, APOE, MAPT0.735$0.72SDA-2026-04-02-gap-0
#88Metabolic Inflexibility Precedes Transcriptional Reprogramming (NAD+/SIRT3 Axis)SIRT3/NAD+ salvage pathway, PGC-1α0.735$0.65SDA-2026-04-06-gap-d
#89Selective Neutral Sphingomyelinase-2 Inhibition TherapySMPD30.731$0.85SDA-2026-04-01-gap-l
#90TREM2 Crosstalk and Synergistic Activation of Phagocytic TranscriptomeTREM2/DAP12 (TYROBP)0.730$0.73SDA-2026-04-06-gap-p
#91Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and NeurograninCHI3L1/TREM2/NRGN0.730$0.73SDA-2026-04-06-gap-d
#92Temporal SPP1 Inhibition During Critical WindowsSPP10.728$0.76SDA-2026-04-15-gap-p
#93Microglial TREM2-Complement Axis ModulationTREM2 and C30.726$0.75SDA-2026-04-03-gap-s
#94Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)CD55 (DAF), CD46 (MCP)0.725$0.73SDA-2026-04-07-gap-p
#95Excessive 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
#96SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 RatioCXCL1, CXCL2, MMP30.720$0.72SDA-2026-04-06-gap-d
#97Microglial IFN-β Priming of Motor Neuron cGAS/STING AmplificationIFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)0.720$0.72SDA-2026-04-07-gap-p
#98AAV-PHP.eB-Mediated Microglial IGFBPL1 ExpressionIGFBPL10.720$0.72SDA-2026-04-06-gap-d
#99NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome PhenotypeNLRP3/CASP1/IL1B0.720$0.72SDA-2026-04-06-gap-p
#100Disease-Associated Microglia Metabolic ReprogrammingTREM20.718$0.67SDA-2026-04-03-gap-s
#101TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial Metabolic FitnessTREM2, TYROBP, SYK, PI3K0.718$0.70SDA-2026-04-02-gap-0
#102Vascular-Glial Interface RestorationCLDN50.716$0.74SDA-2026-04-03-gap-s
#103Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from InflammationTREM2, ADAM10, ADAM170.714$0.70SDA-2026-04-02-gap-0
#104Test: TREM2 enhances amyloid clearance-0.712$0.70-
#105Early Proteasome Restoration TherapyPSMC0.712$0.66SDA-2026-04-03-gap-a
#106APOE4-Specific Microglial Metabolic RescueAPOE, ABCA1, LDLR0.710$0.74SDA-2026-04-04-gap-n
#107Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in Alzheimer's DiseaseTREM20.710$0.71SDA-2026-04-06-gap-p
#108CSF YKL-40 as a Priming-Specific Chitinase MarkerCHI3L1/YKL-400.710$0.71SDA-2026-04-06-gap-d
#109Microglial Disease-Associated States: TREM2-Independent Pathways Driving NeuroinflammationAPOE0.710$0.71SDA-2026-04-02-gap-s
#110TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to RestorativeTREM20.708$0.71SDA-2026-04-07-gap-p
#111Creatine Kinase System Capacity as Neural Energy Reserve BiomarkerCKB0.707$0.70SDA-2026-04-04-gap-d
#112Autophagy-Lysosomal Degradation of IBA1 in Stressed MicrogliaLC3/P62/SQSTM10.706$0.71SDA-2026-04-07-gap-p
#113Test: TREM2 enhances amyloid clearance-0.705$0.70-
#114Ferroptosis Inhibition for α-Synuclein NeuroprotectionGPX40.705$0.73SDA-2026-04-03-gap-a
#115Multiplexed Base Editing for Simultaneous Neuroprotective Gene ActivationSOD1, TARDBP, BDNF, GDNF, IGF-10.704$0.74SDA-2026-04-03-gap-c
#116Microglial Exosome-Mediated Tau PropagationMAPT0.702$0.67SDA-2026-04-03-26abc
#117DAMP-Scavenging Microglial ResetHMGB1, S100 proteins0.701$0.73SDA-2026-04-04-gap-n
#118TREM2 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
#119NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward SenescenceSIRT1/NAMPT/PPARGC1A0.700$0.70SDA-2026-04-06-gap-p
#120SCFA-Producing Bacterial Depletion → Loss of Neuroprotective MicroenvironmentHDAC3, GPR41 (FFAR3), GPR43 (FFAR2), Nrf2, HMOX10.700$0.70sda-2026-04-01-gap-2
#121Granzyme B Inhibition with Serpina3n to Preserve Axonal Integrity Against Cytotoxic AttackGZMB0.698$0.73SDA-2026-04-15-gap-d
#122Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated AmplificationMAPT0.696$0.73SDA-2026-04-03-26abc
#123Temporal Microglial State SwitchingOptogenetic constructs, ion channels0.695$0.73SDA-2026-04-04-gap-n
#124Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial LossCCR20.693$0.69SDA-2026-04-07-gap-p
#125TREM2-Dependent Microglial Surveillance Controls AQP4-Mediated Tau Clearance Through Astrocytic Endfoot MaintenanceTREM20.691$0.74SDA-2026-04-03-26abc
#126TREM2-Mediated Microglial Dysfunction Disrupts Oligodendrocyte Tau Clearance NetworksTREM20.691$0.74SDA-2026-04-03-26abc
#127cGAS-STING Senescence Circuit DisruptionCGAS, STING10.691$0.72SDA-2026-04-03-gap-a
#128H5: BET Bromodomain Readers Sense Aberrant Chromatin and Drive Neuroinflammatory TranscriptionBRD4, BET bromodomains (BRD2/3/4)0.690$0.69SDA-2026-04-04-gap-2
#129TREM2-Dependent Microglial State Transition as Therapeutic Window in Alzheimer's DiseaseTREM2, SYK signaling pathway0.690$0.69SDA-2026-04-02-gap-2
#130Rab27A/B-mediated exosomal tau secretion from microglia drives frontal cortex propagation at Braak III-VIRAB27A0.690$0.69SDA-2026-04-07-gap-d
#131TREM2 Agonism to Rescue APOE4-Induced Microglial DysfunctionTREM20.690$0.69SDA-2026-04-02-gap-a
#132Endothelial 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
#133Astrocyte-Selective APOE4 Silencing via Lipid NanoparticlesAPOE40.682$0.70SDA-2026-04-03-gap-d
#134AQP4 Dysregulation Promotes Neuroinflammation Through Impaired CNS-Peripheral Immune Interface FunctionAQP4; IL6R; CD46 (complement)0.680$0.68SDA-2026-04-07-gap-p
#135Glial Neuroinflammatory Amplification by TDP-43 PathologyTARDBP0.680$0.68SDA-2026-04-08-gap-p
#136CSF Soluble TREM2 Fragment Ratio as Priming State IndicatorTREM2/ADAM10/170.680$0.68SDA-2026-04-06-gap-d
#137Dynamic Lactate-Pyruvate Ratio as Therapeutic Stratification BiomarkerSLC16A10.677$0.67SDA-2026-04-04-gap-d
#138Cell-Type Specific TFEB ModulationTFEB0.677$0.70SDA-2026-04-03-gap-d
#139Astrocyte-Mediated Microglial Memory ErasureGFAP, S100B0.677$0.71SDA-2026-04-04-gap-n
#140Microglial TREM2-Mediated Tau Phagocytosis ImpairmentMAPT0.676$0.72SDA-2026-04-03-26abc
#141White Matter Oligodendrocyte Protection via CXCL10 InhibitionCXCL100.675$0.70SDA-2026-04-03-gap-a
#142Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.672$0.72SDA-2026-04-03-26abc
#143Microglial P2Y12-Dependent Territorial Segregation of Synaptic InputsP2RY12 (P2Y12 receptor)0.670$0.67SDA-2026-04-07-gap-p
#144TREM2 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
#145LPS-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
#146TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition CheckpointTREM2, SYK signaling axis0.668$0.67SDA-2026-04-06-gap-d
#147White Matter Vulnerability Prevention via Oligodendrocyte ProtectionCXCL100.667$0.70SDA-2026-04-03-gap-a
#148Oligodendrocyte DNA Repair Enhancement TherapyPARP1 and XRCC10.665$0.70SDA-2026-04-03-gap-s
#149Peripheral-Central Immune Decoupling TherapyTREM2, complement cascade components0.662$0.69SDA-2026-04-04-gap-n
#150Circadian-Metabolic Microglial ReprogrammingCLOCK, BMAL1, PER20.662$0.69SDA-2026-04-04-gap-n
#151BBB Integrity Loss Defines Absolute Therapeutic Window ClosureMMP-9, Claudin-5, PDGFRβ (pericyte coverage)0.660$0.66SDA-2026-04-06-gap-d
#152Astrocyte IL-1β as Paracrine Mediator of Microglial Complement ExpressionIL1B; IL1R1; MYD880.660$0.66SDA-2026-04-08-gap-p
#153Focused Ultrasound with Microbubble Contrast AgentsIGFBPL10.660$0.66SDA-2026-04-06-gap-d
#154Test: TREM2 enhances amyloid clearance-0.655$0.66-
#155Astrocyte-Microglia Communication Rebalancing via Cytokine ModulationIL1A, TNF, C1Q0.655$0.69SDA-2026-04-03-gap-d
#156Microbiota-Microglia Axis ModulationMultiple0.651$0.68SDA-2026-04-04-gap-2
#157Astrocyte APOE4-Specific Lipid Metabolism CorrectionAPOE0.651$0.69SDA-2026-04-03-gap-s
#158NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Antioxidant DefenseNRF2 (NFE2L2), KEAP10.650$0.62SDA-2026-04-16-gap-f
#159Loss of Homeostatic Epigenetic Identity Reprograms Microglia to Dystrophic StateEZH2/DNMT1/DNMT3A/P2RY12/TMEM1190.650$0.65SDA-2026-04-06-gap-p
#160TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCsRELA (p65), IKBKB (IKKβ)0.650$0.65SDA-2026-04-07-gap-p
#161Galectin-3 deletion attenuates NLRP3 inflammasome activation downstream of lysosomal membrane permeabilizationLGALS30.650$0.65SDA-2026-04-04-gap-l
#162TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling in White Matter NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#163Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading to Senescent Glial NetworksTREM20.649$0.64SDA-2026-04-03-gap-a
#164TREM2-Mediated Mitochondrial Dysfunction in NeurodegenerationTREM20.649$0.64SDA-2026-04-03-gap-a
#165APOE-TREM2 Ligand Availability Dysfunction in NeurodegenerationAPOE0.649$0.64SDA-2026-04-03-gap-a
#166CLU-APOE-TREM2 Tripartite Axis as a Coordinate Therapeutic TargetCLU-APOE-TREM2 axis (LXR/RXR pathway)0.648$0.64SDA-2026-04-14-gap-p
#167Epigenetic Reprogramming of Microglial MemoryDNMT3A, HDAC1/20.647$0.68SDA-2026-04-04-gap-2
#168Inflammatory State-Dependent Ketone TimingIRAKM0.647$0.64SDA-2026-04-03-gap-d
#169NLRP3/Mitophagy Coupling ModulationNLRP30.646$0.67SDA-2026-04-03-gap-i
#170Oligodendrocyte Remyelination EnhancementTREM20.644$0.67SDA-2026-04-03-gap-a
#171Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy-0.644$0.63SDA-2026-04-15-gap-p
#172White Matter Immune Checkpoint RestorationCXCL100.644$0.68SDA-2026-04-03-gap-a
#173Cell-Type Specific Metabolic ReprogrammingPPARA0.643$0.68SDA-2026-04-03-gap-s
#174Epigenetic Silencing of AIF1 Gene Locus by Chronic InflammationDNMT1/DNMT3A0.643$0.64SDA-2026-04-07-gap-p
#175TREM2-Driven Senescence Biomarker Index for Predicting Neurodegeneration RiskTREM20.642$0.64SDA-2026-04-03-gap-a
#176CX3CR1 Promoter Methylation Disrupts Neuron-Microglia Cross-TalkCX3CR10.640$0.64SDA-2026-04-07-gap-d
#177Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progressionGFAP0.640$0.68SDA-2026-04-04-analy
#178Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelopmental FormsSOD1, HTT, TARDBP0.638$0.67SDA-2026-04-03-gap-c
#179Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid PhaseTREM20.637$0.62SDA-2026-04-02-gap-0
#180Test: TREM2 enhances amyloid clearance-0.637$0.64-
#181Vascular mural cell degeneration precedes and exacerbates parenchymal pathologyPDGFRB0.637$0.66SDA-2026-04-04-analy
#182Astrocyte Metabolic Reprogramming via APOE4 CorrectionAPOE0.636$0.67SDA-2026-04-03-gap-s
#183TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection FilterTREM20.636$0.62SDA-2026-04-15-gap-d
#184Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1STAT3/JAK10.633$0.63SDA-2026-04-07-gap-p
#185TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk AlleleTREM20.631$0.61SDA-2026-04-02-gap-0
#186Intestinal 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
#187CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Preventing Template-Dependent MisfoldingCX3CR10.630$0.63SDA-2026-04-04-gap-2
#188Epigenetic Bivalency at CDKN2A Locus Distinguishes Senescent from Activated MicrogliaCDKN2A, H3K9me3, DREAM complex (LIN9, LIN37, RBL2)0.630$0.63SDA-2026-04-06-gap-d
#189Selective Cholinergic Protection via APP Pathway ModulationAPP0.629$0.66SDA-2026-04-03-gap-a
#190Gut-Brain Axis M-Cell ModulationGP2, SPIB0.629$0.66SDA-2026-04-04-gap-n
#191TREM2 Antagonism in Late-Stage Tauopathy — Reducing Neuroinflammatory AmplificationTREM20.628$0.61SDA-2026-04-02-gap-0
#192Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's diseaseTREM20.628$0.67SDA-2026-04-04-analy
#193TREM2 Super-Agonist Induction of DAM Program-0.627$0.63SDA-2026-04-16-gap-2
#194Cardiovascular-Neuroinflammatory Dual TargetingTNF/IL60.627$0.66SDA-2026-04-04-gap-2
#195Peripheral-to-Central Inflammation Circuit BreakerIL1B0.626$0.67SDA-2026-04-16-gap-b
#196Microglial TREM2-Independent Pathway ActivationDAP12, SYK, PLCG20.623$0.66SDA-2026-04-03-gap-d
#197Microglial ACE Enhancement for Amyloid ClearanceACE0.622$0.65SDA-2026-04-03-gap-a
#198Tau 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
#199Microglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutamate ToxicitySLC7A110.620$0.60SDA-2026-04-16-gap-f
#200Cross-Cell Type Synaptic Rescue via Tripartite Synapse RestorationSYN1, SLC1A2, and CX3CR10.620$0.65SDA-2026-04-03-gap-s
#201Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic ShiftHIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)0.620$0.62SDA-2026-04-06-gap-p
#202CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 DeliveryHDAC3 (class I histone deacetylase)0.620$0.62SDA-2026-04-08-gap-d
#203Microglial Metabolic Trained Immunity via mTOR-HIF1α AxisMTOR/HIF1α0.620$0.62SDA-2026-04-07-gap-d
#204Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1C3/C3aR0.618$0.62SDA-2026-04-07-gap-p
#205PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-Induced SPP1 UpregulationSPP10.618$0.62SDA-2026-04-06-gap-p
#206LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP1 InductionSPP10.617$0.62SDA-2026-04-06-gap-p
#207Spatially-Targeted Regional Vulnerability PreventionRegional vulnerability genes0.616$0.65SDA-2026-04-03-gap-s
#208Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic WindowsTFEB, MAPK14, MAPKAPK2, IL6, CXCL10.614$0.61SDA-2026-04-07-gap-d
#209Test: TREM2 enhances amyloid clearance-0.612$0.61-
#210Synaptic Pruning Precision TherapyC1QA, C3, CX3CR1, CX3CL10.612$0.65SDA-2026-04-04-gap-2
#211H2: Perforant Path Synapse Loss via Early Complement Cascade ActivationC1QA, C1QB, C3, ITGAM0.610$0.61SDA-2026-04-02-gap-e
#212Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease PathologymiR-1550.610$0.61SDA-2026-04-06-gap-p
#213Female 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
#214HIF1A stabilization lowers the activation threshold of circadian-disrupted microgliaHIF1A0.609$0.61SDA-2026-04-07-gap-d
#215Microglial priming is primarily epigenetic, with metabolic changes acting as coupled consequences or cofactorsKDM6B0.609$0.61SDA-2026-04-07-gap-d
#216P2RY12-mediated autophagy inhibition in cerebral VSMCs impairs CAA clearanceP2RY120.605$0.60SDA-2026-04-07-gap-p
#217TREM2-Microglial Clearance Enhancement as Common Mechanism for Injury PreventionTREM20.604$0.59SDA-2026-04-14-gap-p
#218mTORC1 Hyperactivation Impairs Autophagic Flux and Drives SenescenceMTOR/TFEB/TFE30.600$0.60SDA-2026-04-06-gap-p
#219TREM2-Mediated Oligodendrocyte-Microglia Cross-talk in White Matter NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#220APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex NeurodegenerationAPOE40.600$0.60SDA-2026-04-06-gap-p
#221TREM2-Dependent Senescent Microglia Disrupt Astrocyte Communication NetworksTREM2/TYROBP0.600$0.54SDA-2026-04-03-gap-a
#222TREM2-Mediated Astroglial Reactivity in NeurodegenerationTREM20.600$0.60SDA-2026-04-03-gap-a
#223Oligodendrocyte-Targeted Myelin Sulfatide Restoration TherapyCST, GAL3ST10.599$0.63SDA-2026-04-03-gap-d
#224OPC differentiation blockade contributes to white matter degeneration in early-stage ADPDGFRA0.599$0.65SDA-2026-04-04-analy
#225Neuronal MHC Class I Expression as a Selectivity DeterminantH2-Kb (H2-K1), Lilrb4 (LilrB2)0.590$0.59SDA-2026-04-07-gap-p
#226Cardiovascular-Neuroinflammation Crosstalk InterruptionIL1B, TNFA, NLRP30.587$0.62SDA-2026-04-04-gap-2
#227TREM2-Mediated Oligodendrocyte-Microglia Signaling in White Matter NeurodegenerationTREM20.587$0.53SDA-2026-04-03-gap-a
#228Senescence-Tau Decoupling TherapyCDKN2A0.585$0.62SDA-2026-04-03-gap-a
#229Gut-Brain Axis Microbiome ModulationGPR43, GPR109A0.585$0.62SDA-2026-04-04-gap-2
#230P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and neurovascular unit dysfunctionP2RY120.585$0.58SDA-2026-04-07-gap-p
#231APOE4 Creates Accelerated, Compressed Reversibility WindowAPOE/TREM2 axis, APOE-TREM2 physical interaction0.584$0.58SDA-2026-04-06-gap-d
#232IGFBPL1-Mediated Homeostatic RestorationIGFBPL10.584$0.62SDA-2026-04-04-gap-2
#233Pharmacological P2RY12 inhibition (ticagrelor/clopidogrel) as repurposing probe for neurovascular outcomesP2RY120.583$0.58SDA-2026-04-07-gap-p
#234Gamma Entrainment Synergy: HBOT-Enhanced Cerebral Perfusion Amplifies SST Interneuron-Targeted Neuromodulation-0.583$0.57SDA-2026-04-16-gap-p
#235ITGAM/CD11b direct binding explains microglial phagocytosis blockadeITGAM0.582$0.58SDA-2026-04-21-gap-d
#236TREM2-Driven Phagocytic Receptor Cascades Determine Mitochondrial Antigen Presentation vs. Intracellular MitophagyTREM20.580$0.58SDA-2026-04-08-gap-p
#237Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement BiosynthesisNFKB1; IKBKB; C1QA; C30.580$0.58SDA-2026-04-08-gap-p
#238TREM2 Promoter Silencing via DNA HypermethylationTREM20.580$0.58SDA-2026-04-07-gap-d
#239Microglial Replacement and Ontogeny ShiftCCR20.580$0.58SDA-2026-04-07-gap-d
#240Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Through Attenuated ChemotaxisP2RY120.580$0.58SDA-2026-04-06-gap-p
#241Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 SignalingNLRP3, LRP1, IL1B, TNF0.580$0.58SDA-2026-04-07-gap-p
#242αvβ3 Integrin-FAK-SYK-CARD9/NF-κB PathwayITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD90.580$0.58SDA-2026-04-06-gap-p
#243Complement-Mediated Synaptic ProtectionC1QA0.580$0.62SDA-2026-04-04-gap-2
#244IGFBPL1-Mediated Microglial ReprogrammingIGFBPL10.579$0.62SDA-2026-04-04-gap-2
#245TREM2-Astrocyte Communication in Microglial DysfunctionTREM20.579$0.00SDA-2026-04-03-gap-a
#246Dynamic Microglial Phenotype Switching Biomarker Panel for Neuroinflammatory Treatment StratificationTREM20.577$0.58SDA-2026-04-16-gap-p
#247TREM2-Senescence Cascade in Astrocyte-Microglia Communication BreakdownTREM20.574$0.00SDA-2026-04-03-gap-a
#248TREM2-P2RY12 Balance Restoration TherapyTREM20.571$0.61SDA-2026-04-04-gap-2
#249Disease-Associated Microglia (DAM) Program Drives IBA1 DownregulationTREM2/TYROBP0.571$0.57SDA-2026-04-07-gap-p
#250PINK1/PARK2-Mediated Mitophagy Enhancement for Neuroinflammation ControlPINK10.571$0.57SDA-2026-04-03-gap-i
#251Neuronal Subtype-Specific Alpha-Synuclein Expression NormalizationSNCA0.571$0.60SDA-2026-04-03-gap-d
#252CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estrogen Receptor-alpha Suppression of NLRP3ESR10.570$0.57SDA-2026-04-06-gap-p
#253Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 InhibitionHDAC6 (class IIb histone deacetylase)0.570$0.57SDA-2026-04-08-gap-d
#254Direct NF-κB Transcriptional Regulation of C1q Genes in MicrogliaRELA; C1QA/C1QB/C1QC0.570$0.57SDA-2026-04-08-gap-p
#255Temporal Gating of Microglial ResponsesCLOCK, ARNTL0.565$0.63SDA-2026-04-04-gap-2
#256Closed-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
#257Closed-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
#258Persistent 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
#259P2X7R PET Imaging for NLRP3 Inflammasome-Associated PrimingP2RX7/NLRP30.560$0.56SDA-2026-04-06-gap-d
#260Test: TREM2 enhances amyloid clearance-0.555$0.55-
#261GluN2B-Mediated Microglial Activation and Tau PropagationGRIN2B0.555$0.56SDA-2026-04-03-26abc
#262Inhibitory Neuron-Selective WNT Signaling RestorationWNT3A, CTNNB1, TCF7L20.554$0.62SDA-2026-04-03-gap-d
#263Profilin-1 Cytoskeletal Checkpoint EnhancementPFN10.554$0.60SDA-2026-04-03-gap-a
#264Dual NF-κB/MMP Inhibition StrategyNFKB10.554$0.57SDA-2026-04-16-gap-b
#265Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation WindowsNLRP30.551$0.55SDA-2026-04-15-gap-p
#266Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional ControlSPP10.551$0.55SDA-2026-04-15-gap-p
#267oxLDL/LOX-1/ROS Signaling Induces P2RY12 via Nrf2 ActivationOLR1 (LOX-1), NFE2L2 (Nrf2)0.550$0.55SDA-2026-04-07-gap-p
#268Surface Exposure of SENP1-β1 Integrin Complex Enables Targeted Senolytic EliminationSENP1, ITGB1 (β1 integrin), ITGAM (CD11b)0.550$0.55SDA-2026-04-06-gap-d
#269Oligodendrocyte DNA Repair EnhancementPARP10.550$0.59SDA-2026-04-03-gap-s
#270Perinatal Hypoxia-Primed Microglia TargetingHIF1A, NFKB10.548$0.59SDA-2026-04-04-gap-2
#271CD300f Immune Checkpoint ActivationCD300F0.545$0.61SDA-2026-04-03-gap-a
#272TREM2-GluN2B Circuit: Microglial Control of Thalamocortical Oscillations and Glymphatic Tau ClearanceTREM20.543$0.00SDA-2026-04-03-26abc
#273Epigenetic 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
#274TAM Receptor (MERTK/AXL) Cross-RegulationMERTK, AXL, TYRO3, PROS1 (Protein S), GAS60.540$0.54SDA-2026-04-06-gap-p
#275P2Y6R 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
#276Synaptic Vulnerability Window Temporal Targeting: Transient SPP1 BlockadeSPP10.540$0.54SDA-2026-04-07-gap-p
#277H5: Olfactory System as a Toxicant Funnel into Layer IINLRP3, CX3CR1, TLR40.540$0.54SDA-2026-04-02-gap-e
#278Soluble 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
#279Test: TREM2 enhances amyloid clearance-0.537$0.54-
#280CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering NF-κB-Dependent SPP1 TranscriptionSPP10.535$0.74SDA-2026-04-06-gap-p
#281NFκB/C1Q SASP Modulation for Synaptic Protection-0.534$0.53SDA-2026-04-16-gap-p
#282TREM2-Mediated Microglial Checkpoint TherapyTREM20.534$0.58SDA-2026-04-03-gap-s
#283TSPO PET Kinetic Modeling for Priming State DiscriminationTSPO0.530$0.53SDA-2026-04-06-gap-d
#284CX3CR1-Targeted AntimiR-155 Oligonucleotides for Microglial Priming ReversalMIR155 (microRNA-155)0.530$0.53SDA-2026-04-08-gap-d
#285TREM2 Epigenetic Window for Microglial Lipid MetabolismTREM2/HDAC10.525$0.53SDA-2026-04-07-gap-d
#286TREM2-Dependent Microglial Control of Thalamocortical-Glymphatic Tau ClearanceTREM20.524$0.00SDA-2026-04-03-26abc
#287TREM2 Agonism to Redirect Microglia from Synaptic Pruning to OPTN-Deficient Neuron ProtectionTREM20.521$0.51SDA-2026-04-14-gap-p
#288M-Sec/TNTA2-mediated tunneling nanotube formation drives glia-neuron tau propagation in mid-stagesTNFAIP20.520$0.52SDA-2026-04-07-gap-d
#289Blood Monocyte Epigenetic Signature as Surrogate for Microglial PrimingEpigenetic landscape (TLR4, NLRP3, IL1B regulatory regions)0.520$0.52SDA-2026-04-06-gap-d
#290Dysregulated 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
#291Loss of Nuclear Lamin B1 Distinguishes Senescent Microglia from Inflammatory ActivationLMNB1 (Lamin B1)0.520$0.52SDA-2026-04-06-gap-d
#292Mitochondrial DNA Damage and cGAS-STING Activation Induces Microglial SenescenceCGAS/STING1/TMEM1730.520$0.52SDA-2026-04-06-gap-p
#293GATA4 Stabilization and NF-κB Co-activation Identifies Senescent MicrogliaGATA4, SQSTM1/p62, NFKB subunits0.520$0.52SDA-2026-04-06-gap-d
#294Telomere Attrition and DNA Damage Response Activation Induces Microglial SenescenceTP53/CDKN2A/CDKN1A/ATM/ATR0.520$0.52SDA-2026-04-06-gap-p
#295Epigenetic Dysregulation of APOE Microglial ExpressionAPOE0.520$0.52SDA-2026-04-07-gap-d
#296miR-143/145 Cluster Dysregulation Derepresses P2RY12 TranscriptionMIR143, MIR145, KLF40.520$0.52SDA-2026-04-07-gap-p
#297Severely Depleted mtDNA and Impaired OXPHOS Defines Senescent MicrogliaMT-ND1, MT-CO1, TFAM, SIRT30.520$0.52SDA-2026-04-06-gap-d
#298Lipid Nanoparticle Encapsulation of IGFBPL1-mRNAIGFBPL10.520$0.52SDA-2026-04-06-gap-d
#299Downstream Pathway Selective Modulation: ITGAX (αXβ2) Integrin BlockadeITGAX (CD11c)0.519$0.52SDA-2026-04-07-gap-p
#300Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late InhibitionSPP10.518$0.52SDA-2026-04-07-gap-p
#301NRF2 Activation to Counteract Oxidative Stress from RGS6 Deficiency-0.518$0.52SDA-2026-04-17-gap-p
#302Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Downregulation via NRF2NRF2/NFE2L20.517$0.52SDA-2026-04-07-gap-p
#303Hippocampus ages transcriptionally faster than cerebellum, defining a regional vulnerability axis conserved across speciesCLU0.516$0.50aging-mouse-brain-20
#304Test: TREM2 enhances amyloid clearance-0.512$0.51-
#305Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated FailureC1Q0.510$0.51SDA-2026-04-02-gap-s
#306Primed microglia occupy a hybrid high-glycolysis and high-respiration metabolic statePDHA10.510$0.51SDA-2026-04-07-gap-d
#307Circulating IBA1 Protein Absorption/Interference with DetectionAIF1/IBA10.507$0.51SDA-2026-04-07-gap-p
#308PKM2 nuclear translocation bridges metabolism and inflammatory transcription in primed microgliaPKM20.506$0.51SDA-2026-04-07-gap-d
#309CX3CR1 PET with Nano-bodies for Microglial Surveillance State MappingCX3CR10.500$0.50SDA-2026-04-06-gap-d
#310LRP1 Loss-of-Function Derepresses P2RY12 ExpressionLRP10.500$0.50SDA-2026-04-07-gap-p
#311Selectively Inhibit Maladaptive AQP4-Driven Astrocyte-Microglia Inflammatory Signaling in Parkinsonian InjuryAQP4, NFKB1, IL1B, TNF0.500$0.50SDA-2026-04-07-gap-p
#312Early Postnatal TGF-beta Signaling Establishes Lifelong Regional Vulnerability Through Irreversible Transcriptional ImprintingTGFBR10.500$0.50SDA-2026-04-06-gap-p
#313Alectinib-C1q Complex Hijacks TREM2's Synaptic Protective Binding InterfaceC1QA/C1QB/C1QC, TREM20.500$0.52SDA-2026-04-16-gap-p
#314TREM2-Mediated Microglial Dysfunction Drives Tau-Induced Blood-Brain Barrier BreakdownTREM20.499$0.00SDA-2026-04-03-26abc
#315TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated Survival and Metabolic SignalingSPP10.496$0.50SDA-2026-04-06-gap-p
#316Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critical Neuroinflammatory WindowsNLRP30.496$0.00SDA-2026-04-15-gap-p
#317TREM2-Mediated Microglial Metabolic Reprogramming Accelerates Tau Pathological SpreadTREM20.494$0.00SDA-2026-04-03-26abc
#318YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Perivascular FibroblastsSPP10.492$0.70SDA-2026-04-06-gap-p
#319GluN2B-Regulated Microglial Phagocytosis of Tau Aggregates via CX3CR1 SignalingGRIN2B0.491$0.00SDA-2026-04-03-26abc
#320P2RY12/P2RY13 Purinergic Receptor Metabolic RewiringP2RY12, P2RY13, CTNNB1 (β-catenin), GSK3β0.490$0.49SDA-2026-04-06-gap-p
#321Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal ExpressionMFGE8, NPTX2 (Neuronal Pentraxin 1)0.490$0.49SDA-2026-04-07-gap-p
#322Testosterone-Derived DHT Amplifies Microglial Androgen Receptor Signaling Driving Male-Biased NeuroinflammationAR0.490$0.49SDA-2026-04-06-gap-p
#323C1q-Mediated Delivery of miR-33 Antisense Oligonucleotides for Enhanced APOE4 LipidationmiR-33a/miR-33b0.489$0.49SDA-2026-04-16-gap-d
#324APOE4 Structural Remodeling via HSP70 Chaperone Enhancement StrategyHSP70/APOE40.486$0.00SDA-2026-04-16-gap-d
#325TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inflammasome RegulationTFEB0.485$0.00SDA-2026-04-03-gap-i
#326PINK1/PARK2-LC3 Mitophagy EnhancementPINK10.485$0.48SDA-2026-04-03-gap-i
#327SIRT3 gates microglial surveillance versus primed metabolism through mitochondrial deacetylationSIRT30.482$0.48SDA-2026-04-07-gap-d
#328Platelet-Derived PDGF-BB Primes VSMCs for P2RY12 UpregulationPDGFB, PDGFRB0.480$0.48SDA-2026-04-07-gap-p
#329Ferroptosis as Context-Dependent and Motor Neuron-Subtype Selective-0.475$0.53SDA-2026-04-18-gap-d
#330Cerebral VSMC foam cells induce pericyte detachment via PDGF-BB/VEGF imbalance, impairing neurovascular couplingP2RY120.473$0.47SDA-2026-04-07-gap-p
#331Intranasal IGFBPL1 Delivery via Olfactory PathwayIGFBPL10.470$0.47SDA-2026-04-06-gap-d
#332CD44-Mediated Src/PI3K/Akt Signaling CascadeCD44, SRC, PI3K p85 (PIK3R1), MTOR0.470$0.47SDA-2026-04-06-gap-p
#333C1Q-Glia Cross-Talk in Vascular Dementia PathogenesisC1QA/C1QC0.470$0.47SDA-2026-04-07-gap-p
#334APOE and TREM2 interact to modulate age-dependent microglial dysfunctionTREM20.467$0.50aging-mouse-brain-20
#335Cross-Tissue Communication DisruptionMULTIPLE0.466$0.51SDA-2026-04-16-gap-b
#336Source-Specific SPP1 Inhibition: Perivascular Cell TargetingSPP1 (perivascular)0.466$0.47SDA-2026-04-07-gap-p
#337TYROBP Network Hyperactivation Marks Point of No ReturnTYROBP/SYK axis, MAPK/ERK signaling0.463$0.46SDA-2026-04-06-gap-d
#338Microglial Priming Window for HDAC1-Dependent DAM TransitionHDAC10.463$0.46SDA-2026-04-07-gap-d
#339Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology into NeuroinflammationMLKL / RIPK10.460$0.46SDA-2026-04-07-gap-p
#340CSF 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
#341Selective Microglial Senescence Targeting via TREM2 ModulationTREM20.459$0.50SDA-2026-04-04-gap-s
#342Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional ControlSPP10.459$0.00SDA-2026-04-15-gap-p
#343C1q Inhibition Prevents Synaptic Mitochondrial Dysfunction via Microglial-Neuronal Cross-Talk NormalizationC1QA/C1QB/C1QC0.455$0.45SDA-2026-04-15-gap-p
#344Mitochondrial Damage-Triggered SPP1 Inflammasome CouplingSPP10.453$0.00SDA-2026-04-15-gap-p
#345α4β1 Integrin (VLA-4) and JAK/STAT PathwayITGA4, ITGB1 (α4β1 heterodimer), JAK1/JAK2, STAT30.450$0.45SDA-2026-04-06-gap-p
#346Monocyte Trojan Horse Cell TherapyIGFBPL10.450$0.45SDA-2026-04-06-gap-d
#347Astrocytic SPP1 Modulation for Neuroinflammatory ResolutionSPP10.447$0.00SDA-2026-04-15-gap-p
#348Microglial Membrane Camouflage Exploits CD47-SIRPα Checkpoint DisinhibitionCD47, SIRPA, PTPN6, PTPN110.444$0.46SDA-2026-04-16-gap-p
#349RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular FibroblastsSPP10.442$0.44SDA-2026-04-06-gap-p
#350DNA Hypomethylation at P2RY12 Promoter Correlates with Disease ProgressionDNMT1, TET20.440$0.44SDA-2026-04-07-gap-p
#351KLF4-Mediated Transcriptional Repression of P2RY12KLF40.440$0.44SDA-2026-04-07-gap-p
#352Test: TREM2 enhances amyloid clearance-0.437$0.44-
#353C1q-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
#354Lactate-HCAR1 signaling maintains a self-reinforcing glycolytic priming loopHCAR10.427$0.43SDA-2026-04-07-gap-d
#355P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription via Calcineurin/NFAT PathwaySPP10.423$0.63SDA-2026-04-06-gap-p
#356C1q-Conjugated miR-33 ASO Brain Delivery for Enhanced APOE4 LipidationmiR-33a/miR-33b0.423$0.00SDA-2026-04-16-gap-d
#357LncRNA-HDAC1 Complex Formation Locks Microglia in Primed StateHDAC1/NEAT10.420$0.45SDA-2026-04-07-gap-d
#358IGFBPL1 Peptide Mimetics for Drug-Like BBB PermeabilityIGFBPL10.420$0.66SDA-2026-04-06-gap-d
#359P2RY12-mediated cerebral VSMC dysfunction establishes a vicious cycle with microglial P2RY12 activationP2RY12 (dual: VSMC + microglia)0.418$0.42SDA-2026-04-07-gap-p
#360C1q-Alectinib Complexation Enhances CNS Penetration via Microglial C1qR-Mediated Uptake and RedistributionC1QBP0.415$0.47SDA-2026-04-17-gap-d
#361Test: TREM2 enhances amyloid clearance-0.405$0.41-
#362Test: TREM2 enhances amyloid clearance-0.400$0.41-
#363Test: TREM2 enhances amyloid clearance-0.400$0.41-
#364Test: TREM2 enhances amyloid clearance-0.400$0.41-
#365Test: TREM2 enhances amyloid clearance-0.400$0.41-
#366Test: TREM2 enhances amyloid clearance-0.400$0.40-
#367CSF1R Inhibition Reversal Window Depends on Microglia Replacement KineticsCSF1R, nestin+ progenitor pool0.395$0.40SDA-2026-04-06-gap-d
#368BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic primingARNTL0.389$0.39SDA-2026-04-07-gap-d
#369Partial Agonist/SPP1 Splice Variant Strategy: Splice-Switching TherapeuticsSPP1 splicing factors0.375$0.41SDA-2026-04-07-gap-p
#370P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via SASP secretionP2RY120.373$0.37SDA-2026-04-07-gap-p
#371Ferroptosis as Epiphenomenon of Terminal Collapse-0.363$0.43SDA-2026-04-18-gap-d
#372Age-related neuroinflammation mimics early Alzheimer's disease pathologyGFAP0.362$0.50aging-mouse-brain-20
#373Ferroptosis as Primary Driver of Motor Neuron Death-0.339$0.40SDA-2026-04-18-gap-d
#374[Archived Hypothesis]-0.300$0.30-
#375[Archived Hypothesis]-0.300$0.30-
#376P2RY12 rs2046934 polymorphism modifies neurodegeneration risk by altering cerebral vascular autophagy capacityP2RY12 (rs2046934)0.273$0.27SDA-2026-04-07-gap-p
#377TREM2 Agonism with CX3CR1 Antagonism for Microglial Homeostasis-0.105$0.17SDA-NEUROINFLAM-BIOM
#378TYROBP Causal Network Inhibition for Microglial Repolarization-0.105$0.20SDA-NEUROINFLAM-BIOM
#379IL-33/ST2 Axis Augmentation for Synaptic Protection-0.105$0.20SDA-NEUROINFLAM-BIOM
#380P2RX7-PANX1 Channel Blockade for Neuroinflammatory Cascade Interruption-0.105$0.20SDA-NEUROINFLAM-BIOM

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