🔥 Neuroinflammation

Cross-disease microglial, astrocyte, and immune hypotheses

Index Score
0.477
Hypotheses
726
Unique Genes
465
Avg Score
0.626

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 targeting EC-II SST interneurons to restore hippocampal gamma oscillations via upstream perforant path gating in Alzheimer's diseaseSST0.968$0.60SDA-2026-04-03-26abc
#2GluN2B-Mediated Thalamocortical Control of Glymphatic Tau ClearanceGRIN2B0.964$0.57SDA-2026-04-03-26abc
#3Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to prevent tau propagation and restore entorhinal-hippocampal gamma synchrony in early Alzheimer's diseaseSST0.955$0.58SDA-2026-04-03-26abc
#4Gamma entrainment therapy to restore hippocampal-cortical synchronySST0.946$0.60SDA-2026-04-03-26abc
#5Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor ImpairmentMAPT0.937$0.55SDA-2026-04-03-26abc
#6Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.924$0.69SDA-2026-04-01-gap-2
#7APOE-Dependent Autophagy RestorationMTOR0.895$0.67SDA-BIOMNI-SURVIVAL-
#8Hypothesis 4: Metabolic Coupling via Lactate-Shuttling CollapseSLC16A1, SLC16A7, LDHA, PDHA10.895$0.59SDA-2026-04-26-gap-p
#9SIRT1-Mediated Reversal of TREM2-Dependent Microglial SenescenceSIRT10.893$0.61SDA-2026-04-03-gap-a
#10TREM2-Mediated Astrocyte-Microglia Crosstalk in NeurodegenerationTREM20.892$0.58SDA-2026-04-03-gap-a
#11ACSL4-Driven Ferroptotic Priming in Disease-Associated MicrogliaACSL40.891$0.59SDA-2026-04-03-gap-s
#12Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially IrreversibleAPP/PSEN1 (Aβ production), CHAT (cholinergic synthesis)0.887$0.60SDA-2026-04-12-20260
#13Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State Transition RestorationIFNG0.887$0.64SDA-2026-04-16-gap-d
#14TREM2-APOE Axis Dissociation for Selective DAM ActivationTREM2-APOE axis0.886$0.64SDA-2026-04-01-gap-0
#15Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilizationBDNF0.885$0.61SDA-2026-04-03-26abc
#16Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling for tau clearanceSST0.884$0.61SDA-2026-04-03-26abc
#17Circadian Glymphatic Entrainment via Targeted Orexin Receptor ModulationHCRTR1/HCRTR20.882$0.61sda-2026-04-01-gap-v
#18Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and block tau AIS disruption in ADPVALB0.869$0.60SDA-2026-04-03-26abc
#19Complement Cascade Inhibition Synaptic Protection-0.867$0.58SDA-2026-04-26-gap-p
#20Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via direct PV interneuron recruitment in Alzheimer's diseasePVALB0.865$0.61SDA-2026-04-03-26abc
#21Glymphatic-Mediated Tau Clearance DysfunctionMAPT0.865$0.60SDA-BIOMNI-PROTEOMI-
#22Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-gamma coupling and prevent tau seeding in ADPVALB0.863$0.56SDA-2026-04-03-26abc
#23TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM TransitionNAMPT0.862$0.66SDA-BIOMNI-VARIANT_-
#24TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau ClearanceTREM20.861$0.59SDA-2026-04-26-trem2
#25Senescent Cell ASM-Complement Cascade InterventionSMPD10.852$0.70SDA-2026-04-01-gap-l
#26Prime Editing Precision Correction of APOE4 to APOE3 in MicrogliaAPOE0.850$0.62SDA-2026-04-03-gap-c
#27TYROBP (DAP12) Conditional Antagonism for Early-Stage NeuroprotectionTYROBP0.844$0.65SDA-BIOMNI-GENE_COE-
#28Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in NeurodegenerationSMPD30.844$0.70SDA-2026-04-01-gap-l
#29miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective Microglial State TransitionMIR1550.843$0.64SDA-2026-04-16-gap-d
#30Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte SecretomeSST, SSTR1, SSTR20.839$0.58SDA-2026-04-26-gap-p
#31Sequential 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$0.60SDA-2026-04-26-gap-p
#32Gamma Oscillation Enhancement Synergy-0.838$0.60SDA-2026-04-26-gap-p
#33Microglial Senescence Prevention via TREM2/SASP AxisTREM20.837$0.58SDA-2026-04-26-gap-p
#34TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism DysregulationTREM2/TYROBP0.836$0.66SDA-2026-04-06-gap-p
#35Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)CD55 (DAF), CD46 (MCP)0.833$0.64SDA-2026-04-07-gap-p
#36AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue responsesPRKAA10.833$0.73sda-2026-04-01-gap-v
#37IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia InterfaceIL6R, IL60.831$0.68SDA-2026-04-13-gap-p
#38Ketone Utilization Index as Metabolic Flexibility BiomarkerHMGCS20.829$0.57SDA-2026-04-04-gap-d
#39Microglial-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.827$0.61SDA-2026-04-03-26abc
#40Real-time gamma-guided transcranial focused ultrasound targeting EC-II SST interneurons to restore hippocampal-prefrontal synchrony in early ADSST0.827$0.56SDA-2026-04-03-26abc
#41Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymphatic enhancement and amyloid clearance from PV interneurons in Alzheimer's diseasePVALB0.827$0.56SDA-2026-04-03-26abc
#42miR-33 Antisense Oligonucleotide Hyper-Lipidation StrategymiR-33/ABCA10.824$0.63SDA-2026-04-16-gap-d
#43Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuroinflammation in ALS/FTDAIM2, CASP1, IL1B, PYCARD, TARDBP0.824$0.67SDA-2026-04-01-gap-2
#44SASP-Mediated Complement Cascade AmplificationC1Q/C30.822$0.61sda-2026-04-01-gap-0
#45Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous NeurodegenerationNLRP3, CASP1, IL1B, PYCARD0.822$0.60SDA-2026-04-01-gap-2
#46STING Antagonists as ALS Therapeutics: Drug RepurposingSTING (TMEM173)0.821$0.62SDA-2026-04-07-gap-p
#47Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservationBDNF0.820$0.65SDA-2026-04-03-26abc
#48Extracellular Vesicle Biogenesis ModulationCHMP4B0.814$0.61SDA-2026-04-04-gap-t
#49TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects SPP1 Signaling from Destructive to RestorativeTREM20.813$0.62SDA-2026-04-07-gap-p
#50CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerability ThresholdsAPOE, CLU0.811$0.60SDA-2026-04-15-gap-d
#51LRP1-Dependent Tau Uptake DisruptionLRP10.808$0.62SDA-2026-04-04-gap-t
#52CSF1R-TREM2 Co-Agonism for Sustained Microglial ExpansionCSF1R-TREM20.808$0.61SDA-2026-04-01-gap-0
#53Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to NeuroinflammationHCAR20.808$0.64SDA-2026-04-15-gap-d
#54Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and NeurograninCHI3L1/TREM2/NRGN0.807$0.62SDA-2026-04-06-gap-d
#55Neutrophil Extracellular Trap (NET) InhibitionPADI40.806$0.69SDA-2026-04-16-gap-b
#56Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.805$0.63SDA-2026-04-01-gap-2
#57Targeted Butyrate Supplementation for Microglial Phenotype ModulationGPR109A0.805$0.58SDA-2026-04-01-gap-2
#58Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD, PPIF0.804$0.60SDA-2026-04-01-gap-2
#59TREM2-mTOR Co-Agonism for Metabolic ReprogrammingTREM2-mTOR pathway0.803$0.60SDA-2026-04-01-gap-0
#60Dual-Receptor Antibody Shuttling-0.803$0.60-
#61Targeting the Mechanistic Link Between AQP4 Dysfunction and Ferroptosis Prevents Both Cytotoxic and Vasogenic Edema After Cardiac ArrestAQP4 and ACSL4 (key ferroptosis regulator)0.803$0.62SDA-2026-04-26-gap-p
#62Mitochondrial DNA-Driven AIM2 Inflammasome Activation in NeurodegenerationAIM2, CASP1, IL1B, PYCARD0.803$0.59SDA-2026-04-01-gap-2
#6340 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated MicrogliaACSL40.801$0.62SDA-2026-04-03-gap-s
#64Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective EffectorMANF, CDNF0.798$0.59SDA-2026-04-26-gap-p
#65Microglial TREM2-SYK Pathway EnhancementTREM20.798$0.59SDA-2026-04-03-gap-s
#66Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)APOE0.795$0.59sda-2026-04-01-gap-0
#67Targeting SASP-Complement Amplification Through HIF-1α Downstream EffectorsC1QA, C1QB, C3, IL1B0.793$0.63SDA-2026-04-13-gap-p
#68Senescent Microglia Resolution via Maresins-Senolytics CombinationBCL2L10.791$0.59sda-2026-04-01-gap-0
#69Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory PrimingTLR40.789$0.68SDA-2026-04-01-gap-2
#70VCP-Mediated Autophagy EnhancementVCP0.787$0.59SDA-2026-04-04-gap-t
#71Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid PathologyCHRNA7 (α7 nicotinic receptor), BACE10.785$0.60SDA-2026-04-12-20260
#72Competitive APOE4 Domain Stabilization PeptidesAPOE0.784$0.60sda-2026-04-01-gap-0
#73Integrated Biomarker Panel for Therapeutic Window IdentificationCHI3L10.784$0.59SDA-2026-04-15-gap-d
#74Closed-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$0.57SDA-2026-04-03-26abc
#75SASP-Driven Aquaporin-4 DysregulationAQP40.782$0.64sda-2026-04-01-gap-0
#76Selective Acid Sphingomyelinase Modulation TherapySMPD10.782$0.65SDA-2026-04-01-gap-l
#77TREM2-mediated microglial tau clearance enhancementTREM20.780$0.59SDA-2026-04-04-gap-t
#78Sleep-Dependent Glymphatic Clearance Expands the Therapeutic Window by Reducing Extracellular Tau BurdenAQP4, orexin receptor (HCRTR1/2)0.780$0.63SDA-2026-04-06-gap-d
#79ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter Degeneration in Alzheimer's DiseaseACSL40.779$0.58SDA-2026-04-03-gap-s
#80PDE4 Inhibition as Inflammatory Reset for PD OligodendrocytesPDE4A, PDE4B, PDE4D0.779$0.62SDA-2026-04-13-gap-p
#81Selective HDAC3 Inhibition with Cognitive EnhancementHDAC30.779$0.71SDA-2026-04-04-gap-e
#82SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microbiome-Induced Neuroinflammation in PDSIRT1, PGC-1α (PPARGC1A), NAMPT0.778$0.60SDA-BIOMNI-MICROBIO-
#83LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine in Disease-Associated MicrogliaLPCAT30.777$0.57SDA-2026-04-03-gap-s
#84CX3CR1-TREM2 Integration for Synapse Pruning NormalizationCX3CR1-TREM20.776$0.60SDA-2026-04-01-gap-0
#85LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Disease-Associated MicrogliaLPCAT30.776$0.55SDA-2026-04-03-gap-s
#86Prefrontal sensory gating circuit restoration via PV interneuron enhancementPVALB0.775$0.65SDA-2026-04-03-26abc
#87Dual-Circuit Tau Vulnerability CascadeMAPT0.774$0.57SDA-2026-04-03-26abc
#88TREM2-APOE4 Co-targeting — Simultaneous Correction of Lipid Sensing and Clearance DeficitsTREM2, APOE0.774$0.62SDA-2026-04-02-gap-0
#89Dual-Domain Antibodies with Engineered Fc-FcRn Affinity ModulationFCGRT0.773$0.58sda-2026-04-01-gap-0
#90ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE PeroxidationALOX150.772$0.57SDA-2026-04-03-gap-s
#91Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory PathwayGPNMB, CD440.772$0.60SDA-2026-04-26-gap-p
#92Enhancing Microglial Phagocytosis of Extracellular Tau via TREM2 ActivationTREM20.771$0.61SDA-2026-04-04-gap-t
#93Oligodendrocyte Precursor Cell Senescence in White Matter DiseaseCSPG4,OLIG2,BCL20.769$0.57SDA-2026-04-04-gap-s
#94Chromatin Accessibility Restoration via BRD4 ModulationBRD40.768$0.60SDA-2026-04-04-gap-e
#95CYP46A1 Overexpression Gene TherapyCYP46A10.768$0.65SDA-2026-04-01-gap-l
#96AAV-PHP.eB-Mediated Microglial IGFBPL1 ExpressionIGFBPL10.768$0.61SDA-2026-04-06-gap-d
#97Lysosomal Cathepsin-Dependent Tau Clearance-0.767$0.62SDA-2026-04-26-gap-p
#98APOE4 Allosteric Rescue via Small Molecule ChaperonesAPOE0.765$0.60sda-2026-04-01-gap-0
#99LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability in Disease-Associated MicrogliaLPCAT30.764$0.61SDA-2026-04-03-gap-s
#100Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes, normalizing cholesterol export and reducing AD-relevant neurotoxicityNR1H2 (LXRβ), ABCA1, ABCG10.763$0.61SDA-2026-04-04-gap-a
#101SASP-Mediated Cholinergic Synapse DisruptionMMP2/MMP90.763$0.63sda-2026-04-01-gap-0
#102Circadian Clock-Autophagy SynchronizationCLOCK0.763$0.59sda-2026-04-01-gap-v
#103Hypothesis 3: HepaCAM-Containing Extracellular VesiclesHEPACAM1, HEPACAM20.762$0.59SDA-2026-04-26-gap-p
#104TREM2 Crosstalk and Synergistic Activation of Phagocytic TranscriptomeTREM2/DAP12 (TYROBP)0.761$0.61SDA-2026-04-06-gap-p
#105Cell-Type Specific TREM2 Upregulation in DAM MicrogliaTREM20.761$0.57analysis-SEAAD-20260
#106cGAS-STING Pathway Hyperactivation Mediates Tau PropagationcGAS (CGAS), STING (TMEM173)0.760$0.62SDA-2026-04-02-gap-2
#107Targeted APOE4-to-APOE3 Base Editing TherapyAPOE0.758$0.64sda-2026-04-01-gap-0
#108INPP5D (SHIP1) Inhibition to Shift Microglial PolarizationINPP5D0.758$0.60SDA-2026-04-01-gap-0
#109APOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporters, driving intracellular lipid droplet accumulation and secondary neuronal cholesterol deficiencyABCA1, ABCG10.758$0.62SDA-2026-04-04-gap-a
#110sTREM2 as Biomarker of Cystatin-C Therapeutic EfficacyTREM20.757$0.68SDA-2026-04-26-gap-p
#111Multi-Modal Stress Response HarmonizationNR3C1/CRH/TNFA0.756$0.57sda-2026-04-01-gap-0
#112Senescence-Activated NAD+ Depletion RescueCD38/NAMPT0.755$0.57sda-2026-04-01-gap-0
#113Test: TREM2 enhances amyloid clearanceTREM20.755$0.59test-hypothesis-fixt
#114GFAP-Positive Reactive Astrocyte Subtype DelineationGFAP0.754$0.59analysis-SEAAD-20260
#115Temporal SPP1 Inhibition During Critical WindowsSPP10.752$0.67SDA-2026-04-15-gap-p
#116Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and restore perforant-path gamma gating in ADSST0.752$0.65SDA-2026-04-03-26abc
#117TREM2-CSF1R Cross-Talk in Microglial Metabolic ReprogrammingTREM2, CSF1R0.748$0.61SDA-2026-04-03-gap-a
#118Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma gating and block tau propagation in ADSST0.748$0.63SDA-2026-04-03-26abc
#119C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV Interneuron Input Elimination in Alzheimer's DiseaseC1QA, C1QB0.747$0.60SDA-2026-04-15-gap-d
#120Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT OverexpressionNAMPT0.745$0.62SDA-2026-04-04-gap-e
#121Circadian-Synchronized Proteostasis EnhancementCLOCK/ULK10.744$0.57sda-2026-04-01-gap-0
#122TREM2-SIRT1 Metabolic Senescence Circuit in Microglial AgingTREM20.744$0.62SDA-2026-04-03-gap-a
#123APOE Isoform Expression Across Glial SubtypesAPOE0.743$0.60analysis-SEAAD-20260
#124Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial LossCCR20.743$0.61SDA-2026-04-07-gap-p
#125Smartphone-Detected Motor Variability CorrectionDRD2/SNCA0.742$0.58sda-2026-04-01-gap-0
#126Senescent Cell Mitochondrial DNA ReleaseCGAS/STING1/DNASE20.742$0.58sda-2026-04-01-gap-0
#127Near-infrared light therapy stimulates COX4-dependent mitochondrial motility enhancementCOX4I10.742$0.59sda-2026-04-01-gap-v
#128APOE4-Selective Lipid Nanoemulsion TherapyAPOE0.742$0.58sda-2026-04-01-gap-a
#129APOE-TREM2 Interaction ModulationTREM20.741$0.58sda-2026-04-01-gap-a
#130Complement-SASP Amplification Cascade as Mechanistic LinkC1QA, C1QB, C3, IL1B, NFKB10.741$0.59SDA-2026-04-16-gap-p
#131Epigenetic Memory Erasure via TET2 ActivationTET20.741$0.58sda-2026-04-01-gap-0
#132PARP1 Inhibition TherapyPARP10.738$0.63sda-2026-04-01-gap-0
#133Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance FateAHR, IL10, TNFRSF13B, TIGIT, FOXP30.738$0.55SDA-2026-04-13-gap-p
#134SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy DysfunctionSIRT30.738$0.57SDA-2026-04-03-gap-s
#135TREM2 Agonism to Restore Microglial Phagocytosis Across Both PathologiesTREM2, TYROBP (DAP12), PLCG2, SYK0.735$0.59SDA-2026-04-16-gap-p
#136Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Antagonist in Tau PhaseTREM2, APOE, MAPT0.735$0.58SDA-2026-04-02-gap-0
#137Metabolic Inflexibility Precedes Transcriptional Reprogramming (NAD+/SIRT3 Axis)SIRT3/NAD+ salvage pathway, PGC-1α0.735$0.58SDA-2026-04-06-gap-d
#138SGMS1-Driven Sphingomyelin Accumulation Impairs BACE1 Lysosomal Degradation via Autophagosome-Lysosome Fusion DysfunctionSGMS1, BECN10.734$0.60SDA-2026-04-15-gap-p
#139Aquaporin-4 Polarization RescueAQP40.732$0.60sda-2026-04-01-gap-0
#140Senescence-Associated Myelin Lipid RemodelingPLA2G6/PLA2G4A0.732$0.55sda-2026-04-01-gap-0
#141Selective Neutral Sphingomyelinase-2 Inhibition TherapySMPD30.731$0.59SDA-2026-04-01-gap-l
#142Senescence-Induced Lipid Peroxidation SpreadingGPX4/SLC7A110.730$0.58sda-2026-04-01-gap-0
#143Adenosine-Astrocyte Metabolic ResetADORA2A0.730$0.58sda-2026-04-01-gap-v
#144Phase-Separated Organelle TargetingG3BP10.729$0.60sda-2026-04-01-gap-0
#145Synthetic Biology BBB Endothelial Cell ReprogrammingTFR1, LRP1, CAV1, ABCB10.727$0.57sda-2026-04-01-gap-0
#146Metabolic Switch Targeting for A1→A2 RepolarizationHK20.726$0.57sda-2026-04-01-gap-0
#147Microglial TREM2-Complement Axis ModulationTREM2 and C30.726$0.60SDA-2026-04-03-gap-s
#148TFAM overexpression creates mitochondrial donor-recipient gradients for directed organelle traffickingTFAM0.725$0.59sda-2026-04-01-gap-v
#149Astrocyte-Mediated Neuronal Epigenetic RescueHDAC0.725$0.57SDA-2026-04-04-gap-e
#150Proteostasis Enhancement via APOE Chaperone TargetingHSPA1A0.724$0.57sda-2026-04-01-gap-a
#151TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN HyperactivationTBK10.724$0.60SDA-2026-04-13-gap-p
#152CSF YKL-40 as a Priming-Specific Chitinase MarkerCHI3L1/YKL-400.723$0.56SDA-2026-04-06-gap-d
#153Interfacial Lipid Mimetics to Disrupt Domain InteractionAPOE0.723$0.58sda-2026-04-01-gap-0
#154Circadian Rhythm Entrainment of Reactive AstrocytesBMAL10.722$0.57sda-2026-04-01-gap-0
#155Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in Alzheimer's DiseaseTREM20.721$0.60SDA-2026-04-06-gap-p
#156Sleep Spindle-Synaptic Plasticity EnhancementCACNA1G0.721$0.57sda-2026-04-01-gap-v
#157Excessive C1q/C3/CR3 complement cascade activation initiates pre-symptomatic synaptic loss in Alzheimer's diseaseC1QA, C1QB, C1QC, C3, ITGAM/ITGAX0.720$0.60SDA-2026-04-02-gap-s
#158H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astrocyte SenescenceABCA1/ABCG1; LXR (NR1H3)0.720$0.60SDA-2026-04-06-gap-d
#159SASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 RatioCXCL1, CXCL2, MMP30.720$0.60SDA-2026-04-06-gap-d
#160Metabolic Reprogramming to Reverse SenescenceSIRT1,PGC1A,NAMPT0.720$0.61SDA-2026-04-04-gap-s
#161Microglial IFN-β Priming of Motor Neuron cGAS/STING AmplificationIFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)0.720$0.61SDA-2026-04-07-gap-p
#162NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome PhenotypeNLRP3/CASP1/IL1B0.720$0.60SDA-2026-04-06-gap-p
#163Stress Granule Phase Separation ModulatorsG3BP10.720$0.67sda-2026-04-01-gap-v
#164Magnetosonic-Triggered Transferrin Receptor ClusteringTFR10.719$0.57sda-2026-04-01-gap-0
#165Retinal Vascular Microcirculation RescuePDGFRB/ANGPT10.718$0.57sda-2026-04-01-gap-0
#166TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial Metabolic FitnessTREM2, TYROBP, SYK, PI3K0.718$0.58SDA-2026-04-02-gap-0
#167APOE Isoform Conversion TherapyAPOE0.718$0.59sda-2026-04-01-gap-a
#168Engineered Apolipoprotein E4-Neutralizing Shuttle PeptidesAPOE, LRP1, LDLR0.718$0.57sda-2026-04-01-gap-0
#169TREM2-Dependent Astrocyte-Microglia Cross-talk in NeurodegenerationTREM20.716$0.60SDA-2026-04-26-trem2
#170Circadian-Synchronized LRP1 Pathway ActivationLRP1, MTNR1A, MTNR1B0.714$0.56sda-2026-04-01-gap-0
#171Soluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from InflammationTREM2, ADAM10, ADAM170.714$0.59SDA-2026-04-02-gap-0
#172Purinergic Signaling Polarization ControlP2RY1 and P2RX70.713$0.58sda-2026-04-01-gap-0
#173TREM2-ASM Crosstalk in Microglial Lysosomal SenescenceSMPD10.713$0.61SDA-2026-04-03-gap-a
#174Test: TREM2 enhances amyloid clearanceTREM20.712$0.59test-hypothesis-fixt
#175Circadian Glymphatic Rescue Therapy (Melatonin-focused)MTNR1A0.712$0.56sda-2026-04-01-gap-v
#176Early Proteasome Restoration TherapyPSMC0.712$0.56SDA-2026-04-03-gap-a
#177Noradrenergic-Tau Propagation BlockadeADRA2A0.711$0.59sda-2026-04-01-gap-v
#178APOE4-Specific Microglial Metabolic RescueAPOE, ABCA1, LDLR0.710$0.60SDA-2026-04-04-gap-n
#179HDAC3-Selective Inhibition for Clock ResetHDAC30.710$0.58sda-2026-04-01-gap-v
#180Microglial Disease-Associated States: TREM2-Independent Pathways Driving NeuroinflammationAPOE0.710$0.60SDA-2026-04-02-gap-s
#181H4: Senomorphic Compounds Preserve Astrocyte Function While Reversing SenescenceMTOR; MEGF10; MERTK0.710$0.60SDA-2026-04-06-gap-d
#182Metabolic Circuit Breaker via Lipid Droplet ModulationPLIN20.709$0.60sda-2026-04-01-gap-0
#183Autophagosome Maturation Checkpoint ControlSTX170.709$0.60sda-2026-04-01-gap-0
#184Matrix Stiffness Normalization via Targeted Lysyl Oxidase InhibitionLOX/LOXL1-40.709$0.59sda-2026-04-01-gap-v
#185TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.708$0.64SDA-2026-04-03-gap-a
#186Membrane Cholesterol Gradient ModulatorsABCA1/LDLR/SREBF20.708$0.59SDA-2026-04-01-gap-l
#187Orexin-Microglia Modulation TherapyHCRTR20.707$0.60sda-2026-04-01-gap-v
#188Creatine Kinase System Capacity as Neural Energy Reserve BiomarkerCKB0.707$0.58SDA-2026-04-04-gap-d
#189TET2-Mediated Demethylation Rejuvenation TherapyTET20.706$0.56sda-2026-04-01-gap-v
#190Lysosomal Enzyme Trafficking CorrectionIGF2R0.706$0.60sda-2026-04-01-gap-0
#191Endothelial Glycocalyx Regeneration via Syndecan-1 UpregulationSDC10.705$0.58sda-2026-04-01-gap-v
#192Test: TREM2 enhances amyloid clearanceTREM20.705$0.64test-hypothesis-fixt
#193Ferroptosis Inhibition for α-Synuclein NeuroprotectionGPX40.705$0.57SDA-2026-04-03-gap-a
#194Microglial Efferocytosis Enhancement via GPR32 SuperagonistsCMKLR10.704$0.56sda-2026-04-01-gap-0
#195Astrocyte-Neuron Metabolic Coupling TitrationBDH10.704$0.59SDA-2026-04-03-gap-d
#196TLR4/MyD88/NF-κB Axis Blockade to Interrupt LPS-Mediated Gut-Brain Neuroinflammation in PDTLR4, MyD88 (MYD88), NF-κB (NFKB1)0.703$0.60SDA-2026-04-16-gap-2
#197Purinergic P2Y12 Inverse Agonist TherapyP2RY120.703$0.57sda-2026-04-01-gap-v
#198Mitochondrial-Nuclear Epigenetic Cross-Talk RestorationSIRT30.701$0.55SDA-2026-04-04-gap-e
#199DAMP-Scavenging Microglial ResetHMGB1, S100 proteins0.701$0.58SDA-2026-04-04-gap-n
#200Microglial Purinergic ReprogrammingP2RY120.701$0.56sda-2026-04-01-gap-0
#201Nutrient-Sensing Epigenetic Circuit ReactivationSIRT10.700$0.63SDA-2026-04-04-gap-e
#202TREM2 haploinsufficiency dysregulates microglial synaptic surveillance, switching from protective 'disease-associated microglia' to neurotoxic 'inflammasome-active' statesTREM2, TYROBP (DAP12), APOE0.700$0.59SDA-2026-04-02-gap-s
#203SCFA-Producing Bacterial Depletion → Loss of Neuroprotective MicroenvironmentHDAC3, GPR41 (FFAR3), GPR43 (FFAR2), Nrf2, HMOX10.700$0.60sda-2026-04-01-gap-2
#204Metabolic Coupling Disruption Sensitizes Motor Neuron mPTP ThresholdPDH (pyruvate dehydrogenase), MCT1/2, PDK, mPTP (ANT/VDAC/Cyclophilin D)0.700$0.59SDA-2026-04-07-gap-p
#205NAD+ Decline and SIRT1 Deficiency Drive Epigenetic Reprogramming Toward SenescenceSIRT1/NAMPT/PPARGC1A0.700$0.59SDA-2026-04-06-gap-p
#206AAV-Mediated APOE2/APOE3 Gene Delivery to Convert APOE GenotypeAPOE0.700$0.60SDA-2026-04-02-gap-a
#207Mechanosensitive Ion Channel ReprogrammingPIEZO1 and KCNK20.700$0.57sda-2026-04-01-gap-0
#208H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective EffectorPXR (NR1I2), IDO10.699$0.64SDA-2026-04-15-gap-p
#209Granzyme B Inhibition with Serpina3n to Preserve Axonal Integrity Against Cytotoxic AttackGZMB0.698$0.60SDA-2026-04-15-gap-d
#210Microglial P2Y12-Dependent Territorial Segregation of Synaptic InputsP2RY12 (P2Y12 receptor)0.697$0.60SDA-2026-04-07-gap-p
#211TFEB-Independent Autophagy BypassULK10.697$0.56SDA-2026-04-03-gap-d
#212Lysosomal Calcium Channel Modulation TherapyMCOLN10.697$0.58sda-2026-04-01-gap-0
#213Perforant Path Presynaptic Terminal Protection StrategyPPARGC1A0.696$0.57sda-2026-04-01-gap-0
#214Axonal RNA Transport ReconstitutionHNRNPA2B10.695$0.58sda-2026-04-01-gap-v
#215Mitochondrial Transfer Pathway EnhancementMIRO10.695$0.57sda-2026-04-01-gap-0
#216Temporal Microglial State SwitchingOptogenetic constructs, ion channels0.695$0.58SDA-2026-04-04-gap-n
#217Complement C1q Mimetic Decoy TherapyC1QA0.695$0.57sda-2026-04-01-gap-v
#218Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene TherapyALOX150.695$0.56sda-2026-04-01-gap-0
#219Palmitoylation-Targeted BACE1 Trafficking DisruptorsBACE10.693$0.55SDA-2026-04-01-gap-l
#220Ocular Immune Privilege ExtensionFOXP3/TGFB10.692$0.56sda-2026-04-01-gap-0
#221Sphingomyelin Synthase Activators for Raft RemodelingSGMS1/SGMS20.692$0.56SDA-2026-04-01-gap-l
#222cGAS-STING Senescence Circuit DisruptionCGAS, STING10.691$0.58SDA-2026-04-03-gap-a
#223Extracellular Matrix Stiffness ModulationPIEZO10.691$0.56sda-2026-04-01-gap-0
#224H5: BET Bromodomain Readers Sense Aberrant Chromatin and Drive Neuroinflammatory TranscriptionBRD4, BET bromodomains (BRD2/3/4)0.690$0.59SDA-2026-04-04-gap-2
#225Rab27A/B-mediated exosomal tau secretion from microglia drives frontal cortex propagation at Braak III-VIRAB27A0.690$0.59SDA-2026-04-07-gap-d
#226TREM2 Agonism to Rescue APOE4-Induced Microglial DysfunctionTREM20.690$0.60SDA-2026-04-02-gap-a
#227Astrocyte Reactivity Heterogeneity with APOE4-Dependent VulnerabilityAPOE0.690$0.59SDA-2026-04-02-gap-s
#228Astrocyte-Neuron Metabolic Coupling Failure Precedes Neurodegeneration in FTD-GRNGRN, SLC16A3 (MCT4)0.690$0.60SDA-2026-04-02-gap-2
#229Loss of AQP4 Polarization Impairs Glymphatic Perivascular Influx, Causing Metabolite AccumulationAQP40.690$0.59SDA-2026-04-07-gap-p
#230TREM2-Dependent Microglial State Transition as Therapeutic Window in Alzheimer's DiseaseTREM2, SYK signaling pathway0.690$0.59SDA-2026-04-02-gap-2
#231Ganglioside Rebalancing TherapyST3GAL2/ST8SIA10.690$0.54SDA-2026-04-01-gap-l
#232CSF Soluble TREM2 Fragment Ratio as Priming State IndicatorTREM2/ADAM10/170.689$0.59SDA-2026-04-06-gap-d
#233Endothelial NRF2 Activation as a Master Switch for Post-CA BBB ProtectionNRF2 (NFE2L2) in brain microvascular endothelial cells0.689$0.62SDA-2026-04-26-gap-p
#234Reelin-Mediated Cytoskeletal Stabilization ProtocolRELN0.689$0.58sda-2026-04-01-gap-0
#235Cross-Seeding Prevention StrategyTARDBP0.689$0.58sda-2026-04-01-gap-v
#236Hypocretin-Neurogenesis Coupling TherapyHCRT0.688$0.57sda-2026-04-01-gap-v
#237Lysosomal Positioning Dynamics ModulationLAMP10.686$0.56sda-2026-04-01-gap-0
#238TREM2 Conformational Stabilizers for Synaptic DiscriminationTREM20.685$0.57sda-2026-04-01-gap-v
#239Pericyte Contractility Reset via Selective PDGFR-β AgonismPDGFRB0.684$0.55sda-2026-04-01-gap-v
#240Focused Ultrasound with Microbubble Contrast AgentsIGFBPL10.684$0.60SDA-2026-04-06-gap-d
#241Astrocyte-Selective APOE4 Silencing via Lipid NanoparticlesAPOE40.682$0.58SDA-2026-04-03-gap-d
#242Context-Dependent CRISPR Activation in Specific Neuronal SubtypesCell-type-specific essential genes0.682$0.55SDA-2026-04-03-gap-c
#243Flotillin-1 Stabilization CompoundsFLOT10.681$0.54SDA-2026-04-01-gap-l
#244Autophagy-Lysosomal Degradation of IBA1 in Stressed MicrogliaLC3/P62/SQSTM10.681$0.58SDA-2026-04-07-gap-p
#245CRISPR-Mediated Mitochondrial Genome Editing for Complex I DysfunctionMT-ND1, MT-ND4, MT-ND60.681$0.56SDA-2026-04-03-gap-c
#246NLRP3/Mitophagy Coupling ModulationNLRP30.681$0.57SDA-2026-04-03-gap-i
#247TREM2 R47H variant synergizes with APOE4 to collapse microglial lipid clearance capacity, causing extracellular lipid accumulation that feeds back to astrocyte lipid droplet formationTREM2, APOE0.681$0.60SDA-2026-04-04-gap-a
#248R-Loop Resolution Enhancement TherapySETX0.680$0.56sda-2026-04-01-gap-v
#249Chaperone-Mediated APOE4 Refolding EnhancementHSPA1A, HSP90AA1, DNAJB1, FKBP50.680$0.56sda-2026-04-01-gap-0
#250Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid PlexusAQP10.680$0.55sda-2026-04-01-gap-v
#251Oligodendrocyte Protectin D1 Mimetic for Myelin ResolutionGPR370.680$0.56sda-2026-04-01-gap-0
#252AQP4 Dysregulation Promotes Neuroinflammation Through Impaired CNS-Peripheral Immune Interface FunctionAQP4; IL6R; CD46 (complement)0.680$0.59SDA-2026-04-07-gap-p
#253Glial Neuroinflammatory Amplification by TDP-43 PathologyTARDBP0.680$0.59SDA-2026-04-08-gap-p
#254......0.680$0.54SDA-2026-04-02-gap-a
#255GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis BlockadeGPX40.680$0.58SDA-2026-04-16-gap-f
#256Astrocytic Connexin-43 Upregulation Enhances Neuroprotective Mitochondrial DonationGJA10.679$0.52SDA-2026-04-01-gap-2
#257Complement C1QA Spatial Gradient in Cortical LayersC1QA0.678$0.55analysis-SEAAD-20260
#258Dynamic Lactate-Pyruvate Ratio as Therapeutic Stratification BiomarkerSLC16A10.677$0.54SDA-2026-04-04-gap-d
#259Cell-Type Specific TFEB ModulationTFEB0.677$0.58SDA-2026-04-03-gap-d
#260Astrocyte-Mediated Microglial Memory ErasureGFAP, S100B0.677$0.57SDA-2026-04-04-gap-n
#261Selective Tau Kinase Inhibition in Vulnerable Neuronal SubtypesMAPT0.676$0.57SDA-2026-04-03-gap-s
#262Microglial TREM2-Mediated Tau Phagocytosis ImpairmentMAPT0.676$0.57SDA-2026-04-03-26abc
#263White Matter Oligodendrocyte Protection via CXCL10 InhibitionCXCL100.675$0.58SDA-2026-04-03-gap-a
#264Excitatory Neuron Vulnerability via SLC17A7 DownregulationSLC17A70.675$0.56analysis-SEAAD-20260
#265RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo deliveryRAB27A0.674$0.53sda-2026-04-01-gap-v
#266Metabolic Reprogramming via Microglial Glycolysis InhibitionHK20.672$0.56sda-2026-04-01-gap-v
#267Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 SignalingTREM20.672$0.57SDA-2026-04-03-26abc
#268Partial Neuronal Reprogramming via Modified Yamanaka CocktailOCT40.672$0.56SDA-2026-04-04-gap-e
#269AQP4-Dependent Astrocyte Swelling Exacerbates Excitotoxic Neuronal Death via Dysfunction of the Glutamate-Gln CycleAQP4; SLC1A2 (GLT-1)0.670$0.58SDA-2026-04-07-gap-p
#270Restore AQP4 Perivascular Polarization by Stabilizing DAPC/SNTA1/DAG1 Anchoring ComplexAQP4, SNTA1, DAG10.670$0.59SDA-2026-04-07-gap-p
#271LPS-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$0.59SDA-2026-04-02-gap-s
#272TREM2 R47H Metabolic Lock-in at Cholesterol Ester AccumulationTREM2/ACAT1/LXR0.670$0.58SDA-2026-04-15-gap-d
#273Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory CommunicationCHRNA70.669$0.55SDA-2026-04-01-gap-2
#274Astrocyte MCT1/MCT4 Ratio Disruption with Metabolic UncouplingSLC16A10.668$0.55SDA-2026-04-03-gap-s
#275Locus Coeruleus-Hippocampal Circuit ProtectionMAPT0.668$0.56SDA-2026-04-03-26abc
#276TREM2 Agonism Has Narrow Early-Window at DAM1→DAM2 Transition CheckpointTREM2, SYK signaling axis0.668$0.58SDA-2026-04-06-gap-d
#277Aquaporin-4 Polarization Enhancement via TREK-1 Channel ModulationKCNK20.668$0.55sda-2026-04-01-gap-v
#278Mitochondrial-Lysosomal Contact Site EngineeringRAB7A0.668$0.55sda-2026-04-01-gap-0
#279White Matter Vulnerability Prevention via Oligodendrocyte ProtectionCXCL100.667$0.57SDA-2026-04-03-gap-a
#280TREM2-Mediated Cholesterol Dysregulation in Microglial SenescenceCYP46A10.666$0.59SDA-2026-04-03-gap-a
#281Lipid Droplet Dynamics as Phenotype SwitchesDGAT1 and SOAT10.666$0.56sda-2026-04-01-gap-0
#282GAP43-mediated tunneling nanotube stabilization enhances neuroprotective mitochondrial transferGAP430.666$0.57sda-2026-04-01-gap-v
#283Glymphatic-Cholinergic Tau Clearance CascadeMAPT0.666$0.56SDA-2026-04-03-26abc
#284Oligodendrocyte DNA Repair Enhancement TherapyPARP1 and XRCC10.665$0.57SDA-2026-04-03-gap-s
#285Complement C1q Subtype SwitchingC1QA0.665$0.57sda-2026-04-01-gap-0
#286TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between SASP and Synaptic PruningTNF, IL1B → GJA1 → C1Q/C30.663$0.55SDA-2026-04-12-gap-d
#287RNA Granule Nucleation Site ModulationG3BP10.662$0.58sda-2026-04-01-gap-0
#288Peripheral-Central Immune Decoupling TherapyTREM2, complement cascade components0.662$0.59SDA-2026-04-04-gap-n
#289Circadian-Metabolic Microglial ReprogrammingCLOCK, BMAL1, PER20.662$0.57SDA-2026-04-04-gap-n
#290Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I Interferon SignalingcGAS (CGAS) / STING (TMEM173) / IFNAR1/20.661$0.58SDA-2026-04-07-gap-p
#291Vascular mural cell degeneration precedes and exacerbates parenchymal pathologyPDGFRB0.661$0.56SDA-2026-04-04-analy
#292Biorhythmic Interference via Controlled Sleep OscillationsGABRA10.661$0.56sda-2026-04-01-gap-0
#293BBB Integrity Loss Defines Absolute Therapeutic Window ClosureMMP-9, Claudin-5, PDGFRβ (pericyte coverage)0.660$0.57SDA-2026-04-06-gap-d
#294SASP Modulation Rather Than Cell EliminationNFKB1,IL1B,BDNF0.660$0.60SDA-2026-04-04-gap-s
#295Complement C1QA Inhibition Synergizes with PV Interneuron ModulationC1QA, PVALB0.659$0.54SDA-2026-04-13-gap-p
#296Astrocyte IL-1β as Paracrine Mediator of Microglial Complement ExpressionIL1B; IL1R1; MYD880.658$0.58SDA-2026-04-08-gap-p
#297TREM2 Activation as an Amplification Node for R136S ProtectionTREM20.657$0.56SDA-2026-04-13-gap-p
#298Temporal TET2-Mediated Hydroxymethylation CyclingTET20.657$0.55SDA-2026-04-04-gap-e
#299Mitochondrial RNA Granule Rescue PathwaySYNCRIP0.656$0.55sda-2026-04-01-gap-v
#300Time-Dependent BBB Repair StrategyMULTIPLE0.656$0.59SDA-2026-04-16-gap-b
#301Optogenetic Microglial Deactivation via Engineered Inhibitory OpsinsCX3CR10.655$0.56sda-2026-04-01-gap-v
#302Test: TREM2 enhances amyloid clearanceTREM20.655$0.60test-hypothesis-fixt
#303Astrocyte-Microglia Communication Rebalancing via Cytokine ModulationIL1A, TNF, C1Q0.655$0.57SDA-2026-04-03-gap-d
#304Arginine Methylation Enhancement TherapyPRMT10.653$0.60sda-2026-04-01-gap-0
#305Microbial Inflammasome Priming PreventionNLRP3, CASP1, IL1B, PYCARD0.653$0.66SDA-2026-04-01-gap-2
#306KDM6A-Mediated H3K27me3 RejuvenationKDM6A0.653$0.57sda-2026-04-01-gap-v
#307Nucleolar Stress Response NormalizationNPM10.653$0.56sda-2026-04-01-gap-v
#308The Mitochondrial-Lysosomal Metabolic Coupling DysfunctionTFEB0.652$0.54SDA-2026-04-02-gap-v
#309SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and Links Synaptic Dysfunction to SASP-Complement ActivationSUMO1, SYT1, C1QA, C30.652$0.58SDA-2026-04-16-gap-d
#310Microbiota-Microglia Axis ModulationMultiple0.651$0.54SDA-2026-04-04-gap-2
#311Astrocyte APOE4-Specific Lipid Metabolism CorrectionAPOE0.651$0.56SDA-2026-04-03-gap-s
#312C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic LoopC3AR1, C3, NFKB10.651$0.60SDA-2026-04-14-gap-p
#313Mitochondrial Calcium Buffering Enhancement via MCU ModulationMCU0.650$0.55sda-2026-04-01-gap-0
#314NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Antioxidant DefenseNRF2 (NFE2L2), KEAP10.650$0.56SDA-2026-04-16-gap-f
#315Loss of Homeostatic Epigenetic Identity Reprograms Microglia to Dystrophic StateEZH2/DNMT1/DNMT3A/P2RY12/TMEM1190.650$0.57SDA-2026-04-06-gap-p
#316TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCsRELA (p65), IKBKB (IKKβ)0.650$0.57SDA-2026-04-07-gap-p
#317Pharmacologically Boost AQP4X Readthrough to Restore Perivascular ClearanceAQP4, AQP4X0.650$0.58SDA-2026-04-07-gap-p
#318NeuroD1-Mediated Astrocyte Reprogramming Attenuates Neuroinflammation Through Epigenetic Remodeling of A1 Astrocyte Signature GenesNeuroD1/NF-kB0.650$0.58SDA-2026-04-04-gap-2
#319APOE-Mediated Synaptic Lipid Raft StabilizationSPTLC10.649$0.54sda-2026-04-01-gap-a
#320Glial Glycocalyx Remodeling TherapyHSPG20.649$0.55sda-2026-04-01-gap-0
#321CX3CR1 Promoter Methylation Disrupts Neuron-Microglia Cross-TalkCX3CR10.649$0.58SDA-2026-04-07-gap-d
#322Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication Leading to Senescent Glial NetworksTREM20.649$0.55SDA-2026-04-03-gap-a
#323TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling in White Matter NeurodegenerationTREM20.649$0.55SDA-2026-04-03-gap-a
#324APOE-TREM2 Ligand Availability Dysfunction in NeurodegenerationAPOE0.649$0.55SDA-2026-04-03-gap-a
#325Apoptosis-Senescence Decision Point InterventionTP53,BAX,BAK1,CASP30.649$0.57SDA-2026-04-04-gap-s
#326IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage ReprogrammingIL10, CSF1R, CD400.648$0.55SDA-2026-04-13-gap-p
#327CLU-APOE-TREM2 Tripartite Axis as a Coordinate Therapeutic TargetCLU-APOE-TREM2 axis (LXR/RXR pathway)0.648$0.57SDA-2026-04-14-gap-p
#328DNMT1-Targeting Antisense Oligonucleotide ResetDNMT10.648$0.55sda-2026-04-01-gap-v
#329HCN1-Mediated Resonance Frequency Stabilization TherapyHCN10.648$0.54sda-2026-04-01-gap-0
#330Mitochondrial SPM Synthesis Platform EngineeringALOX50.647$0.53sda-2026-04-01-gap-0
#331Epigenetic Reprogramming of Microglial MemoryDNMT3A, HDAC1/20.647$0.57SDA-2026-04-04-gap-2
#332Inflammatory State-Dependent Ketone TimingIRAKM0.647$0.56SDA-2026-04-03-gap-d
#333Grid Cell-Specific Metabolic Reprogramming via IDH2 EnhancementIDH20.646$0.55sda-2026-04-01-gap-0
#334Activity-Dependent Synaptic Tagging via CREB-BDNF-TrkB SignalingCREB1, BDNF, NTRK2 (TrkB)0.646$0.58SDA-2026-04-07-gap-p
#335Synthetic Biology Rewiring via Orthogonal ReceptorsCNO0.645$0.56sda-2026-04-01-gap-0
#336Ephrin-B2/EphB4 Axis ManipulationEPHB40.645$0.55sda-2026-04-01-gap-0
#337Oligodendrocyte Remyelination EnhancementTREM20.644$0.58SDA-2026-04-03-gap-a
#338Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy-0.644$0.56SDA-2026-04-15-gap-p
#339Microglial Metabolic Trained Immunity via mTOR-HIF1α AxisMTOR/HIF1α0.644$0.58SDA-2026-04-07-gap-d
#340H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from Synapse Pruning to Amyloid ClearanceTREM20.644$0.57SDA-2026-04-26-trem2
#341White Matter Immune Checkpoint RestorationCXCL100.644$0.56SDA-2026-04-03-gap-a
#342Cell-Type Specific Metabolic ReprogrammingPPARA0.643$0.54SDA-2026-04-03-gap-s
#343Epigenetic Silencing of AIF1 Gene Locus by Chronic InflammationDNMT1/DNMT3A0.643$0.58SDA-2026-04-07-gap-p
#344SASP-Driven Microglial Metabolic Reprogramming in Synaptic PhagocytosisHK2/PFKFB30.643$0.65sda-2026-04-01-gap-0
#345TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.642$0.76SDA-2026-04-03-gap-a
#346TREM2-Mediated Mitochondrial Dysfunction in NeurodegenerationTREM20.642$0.54SDA-2026-04-03-gap-a
#347TREM2-Driven Senescence Biomarker Index for Predicting Neurodegeneration RiskTREM20.642$0.55SDA-2026-04-03-gap-a
#348Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-SeedingCSGA0.642$0.54SDA-2026-04-01-gap-2
#349Glycine-Rich Domain Competitive InhibitionTARDBP0.640$0.56sda-2026-04-01-gap-0
#350Colonic Th17/IL-17A Axis → Peripheral Immune Recruitment to SN and Neuronal ApoptosisRORC (RORγt), IL17A, IL17RA, IL17RC, CXCL9, CXCL10, CXCR3, CD8A0.640$0.57sda-2026-04-01-gap-2
#351Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progressionGFAP0.640$0.55SDA-2026-04-04-analy
#352Transglutaminase-2 Cross-Linking Inhibition StrategyTGM20.639$0.56SDA-2026-04-01-gap-9
#353Mitochondrial NAD+ Salvage EnhancementSTING10.639$0.55SDA-2026-04-03-gap-a
#354Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelopmental FormsSOD1, HTT, TARDBP0.638$0.56SDA-2026-04-03-gap-c
#355Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid PhaseTREM20.637$0.58SDA-2026-04-02-gap-0
#356Test: TREM2 enhances amyloid clearanceTREM20.637$0.60test-hypothesis-fixt
#357Astrocyte Metabolic Reprogramming via APOE4 CorrectionAPOE0.636$0.58SDA-2026-04-03-gap-s
#358TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection FilterTREM20.636$0.58SDA-2026-04-15-gap-d
#359HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.634$0.61SDA-2026-04-04-gap-t
#360Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1STAT3/JAK10.633$0.57SDA-2026-04-07-gap-p
#361Palmitoylethanolamide-Based Endocannabinoid TherapyPPARA0.633$0.54SDA-2026-04-16-gap-b
#362TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk AlleleTREM20.631$0.57SDA-2026-04-02-gap-0
#363Disease-Associated Microglia Metabolic ReprogrammingTREM20.631$0.57SDA-2026-04-03-gap-s
#364C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque MacrophagesC1QA/C1QC0.631$0.56SDA-2026-04-07-gap-p
#365FOXO3-Longevity Pathway Epigenetic ReprogrammingFOXO30.630$0.55sda-2026-04-01-gap-v
#366Epigenetic Bivalency at CDKN2A Locus Distinguishes Senescent from Activated MicrogliaCDKN2A, H3K9me3, DREAM complex (LIN9, LIN37, RBL2)0.630$0.57SDA-2026-04-06-gap-d
#367Intestinal Permeability Defects → Systemic LPS Translocation → Microglial PrimingTight junction complex (CLDN1, OCLN, TJP1), LBP, CD14, TLR4, MYD88, NFKB10.630$0.57sda-2026-04-01-gap-2
#368Programmable Neuronal Circuit Repair via Epigenetic CRISPRNURR1, PITX3, neuronal identity transcription factors0.630$0.52SDA-2026-04-03-gap-c
#369CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Preventing Template-Dependent MisfoldingCX3CR10.630$0.57SDA-2026-04-04-gap-2
#370Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoot Repair in NMOSDAQP4, IL6R, CD19, C50.630$0.57SDA-2026-04-07-gap-p
#371Selective Cholinergic Protection via APP Pathway ModulationAPP0.629$0.58SDA-BIOMNI-CLINICAL-
#372Gut-Brain Axis M-Cell ModulationGP2, SPIB0.629$0.56SDA-2026-04-04-gap-n
#373APOE4-Driven Astrocyte Senescence as Primary TargetAPOE,CDKN1A,BCL2L10.629$0.56SDA-2026-04-04-gap-s
#374Multi-Modal CRISPR Platform for Simultaneous Editing and MonitoringDisease-causing mutations with integrated reporters0.629$0.52SDA-2026-04-03-gap-c
#375TREM2 Antagonism in Late-Stage Tauopathy — Reducing Neuroinflammatory AmplificationTREM20.628$0.59SDA-2026-04-02-gap-0
#376Quantum Coherence Disruption in Cellular CommunicationTUBB30.627$0.54sda-2026-04-01-gap-0
#377Cardiovascular-Neuroinflammatory Dual TargetingTNF/IL60.627$0.55SDA-2026-04-04-gap-2
#378TREM2 Super-Agonist Induction of DAM ProgramTREM20.627$0.54SDA-2026-04-16-gap-2
#379Default Mode Network Circuit StabilizationVIP0.627$0.54SDA-2026-04-03-26abc
#380Peripheral-to-Central Inflammation Circuit BreakerIL1B0.626$0.57SDA-2026-04-16-gap-b
#381Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's diseaseTREM20.626$0.57SDA-2026-04-04-analy
#382TREM2-Mediated Astrocyte-Microglia Cross-Talk in NeurodegenerationTREM20.625$0.76SDA-2026-04-03-gap-a
#383Heat Shock Protein 70 Disaggregase AmplificationHSPA1A0.625$0.56sda-2026-04-01-gap-0
#384Synaptic Phosphatidylserine Masking via Annexin A1 MimeticsANXA10.625$0.54sda-2026-04-01-gap-v
#385Galectin-3 deletion attenuates NLRP3 inflammasome activation downstream of lysosomal membrane permeabilizationLGALS30.625$0.56SDA-2026-04-04-gap-l
#386Autophagy-Senescence Axis Therapeutic WindowATG7,BCL2,BCL2L10.624$0.58SDA-2026-04-04-gap-s
#387Serine/Arginine-Rich Protein Kinase ModulationSRPK10.624$0.53sda-2026-04-01-gap-0
#388Myelin Sulfatide RestorationGAL3ST10.623$0.56SDA-2026-04-03-gap-a
#389TFEB-PGC1α Mitochondrial-Lysosomal DecouplingTFEB0.622$0.53SDA-2026-04-03-gap-a
#390Cholesterol-CRISPR Convergence Therapy for NeurodegenerationHMGCR, LDLR, APOE regulatory regions0.622$0.54SDA-2026-04-03-gap-c
#391Pharmacological Enhancement of APOE4 GlycosylationST6GAL1, FUT80.622$0.52sda-2026-04-01-gap-0
#392Microglial ACE Enhancement for Amyloid ClearanceACE0.622$0.55SDA-2026-04-03-gap-a
#393Vagal Afferent Microbial Signal ModulationGLP1R, BDNF0.621$0.55SDA-2026-04-01-gap-2
#394Designer TRAK1-KIF5 fusion proteins accelerate therapeutic mitochondrial deliveryTRAK1_KIF5A0.621$0.54sda-2026-04-01-gap-v
#395Sphingolipid Metabolism ReprogrammingCERS20.620$0.54sda-2026-04-01-gap-0
#396Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic ShiftHIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)0.620$0.57SDA-2026-04-06-gap-p
#397Cross-Cell Type Synaptic Rescue via Tripartite Synapse RestorationSYN1, SLC1A2, and CX3CR10.620$0.56SDA-2026-04-03-gap-s
#398TREM2 Agonism to Reprogram Infiltrated Monocytes Toward Neuroprotective PhenotypeTREM20.620$0.56SDA-2026-04-13-gap-d
#399Tau fibrils expose neuronal phosphatidylserine and heat-shock protein 70, driving microglial non-complement synaptic engulfment in primary tauopathiesPhosphatidylserine, TIMD4, HSPA1A/HSPA1B, SCARF1, LRP80.620$0.57SDA-2026-04-02-gap-s
#400Microglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutamate ToxicitySLC7A110.620$0.55SDA-2026-04-16-gap-f
#401Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 inflammasome activation without impairing normal proteolysisCTSB0.620$0.57SDA-2026-04-04-gap-l
#402C1Q-Induced Foam Cell Formation via Scavenger Receptor UpregulationC1QA/C1QC0.620$0.56SDA-2026-04-07-gap-p
#403CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 DeliveryHDAC3 (class I histone deacetylase)0.620$0.56SDA-2026-04-08-gap-d
#404Lysosomal pH Restoration Upstream of TFEBATP6V1A0.619$0.56SDA-2026-04-03-gap-d
#405TREM2-Dependent Microglial Senescence TransitionTREM20.618$0.55SDA-BIOMNI-SCRNA_AN-
#406Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1C3/C3aR0.618$0.56SDA-2026-04-07-gap-p
#407TREM2-mediated microglial tau clearance enhancementTREM20.618$0.67SDA-2026-04-04-gap-t
#408Low Complexity Domain Cross-Linking InhibitionTGM20.617$0.54sda-2026-04-01-gap-0
#409LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP1 InductionSPP10.617$0.56SDA-2026-04-06-gap-p
#410Perinatal Immune Challenge PreventionMultiple0.616$0.53SDA-2026-04-04-gap-2
#411Spatially-Targeted Regional Vulnerability PreventionRegional vulnerability genes0.616$0.54SDA-2026-04-03-gap-s
#412Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic WindowsTFEB, MAPK14, MAPKAPK2, IL6, CXCL10.614$0.56SDA-2026-04-07-gap-d
#413Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory CascadeAGER0.613$0.52SDA-2026-04-01-gap-2
#414Trinucleotide Repeat Sequestration via CRISPR-Guided RNA TargetingHTT, DMPK, repeat-containing transcripts0.613$0.55SDA-2026-04-03-gap-c
#415Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic EngineeringTDC0.612$0.53SDA-2026-04-01-gap-2
#416SIRT6-NAD+ Axis Enhancement TherapySIRT60.612$0.54sda-2026-04-01-gap-v
#417Complement-Mediated Synaptic Pruning DysregulationC1QA0.612$0.53SDA-2026-04-03-gap-a
#418Test: TREM2 enhances amyloid clearanceTREM20.612$0.58test-hypothesis-fixt
#419Synaptic Pruning Precision TherapyC1QA, C3, CX3CR1, CX3CL10.612$0.57SDA-2026-04-04-gap-2
#420HDAC3-Dependent A1 Astrocyte Commitment WindowHDAC30.611$0.56SDA-2026-04-07-gap-d
#421Epigenetic Memory Reprogramming for Alzheimer's DiseaseBDNF, CREB1, synaptic plasticity genes0.611$0.55SDA-2026-04-03-gap-c
#422APOE4-Lipid Metabolism CorrectionAPOE0.610$0.56SDA-2026-04-04-gap-2
#423Astrocyte LRP1-mediated tau uptake and APOE4-dependent secretion creates regional susceptibility gradientsLRP10.610$0.56SDA-2026-04-07-gap-d
#424Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease PathologymiR-1550.610$0.56SDA-2026-04-06-gap-p
#425H1: Senolytic Clearance of Senescent APOE4 AstrocytesCDKN2A (p16Ink4a)0.610$0.56SDA-2026-04-06-gap-d
#426Female 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$0.56SDA-2026-04-02-gap-s
#427APOE4 preferentially signals through LRP1 over LDLR, altering endosomal cholesterol trafficking and causing lysosomal cholesterol sequestration that drives lysosomal dysfunction and inflammationLRP1, NPC1, CTSD0.610$0.56SDA-2026-04-04-gap-a
#428H2: Perforant Path Synapse Loss via Early Complement Cascade ActivationC1QA, C1QB, C3, ITGAM0.610$0.56SDA-2026-04-02-gap-e
#429Aberrant Galectin-3 Expression on Stressed Synapses Creates Bridging MoleculesLGALS3 (Galectin-3)0.610$0.57SDA-2026-04-07-gap-p
#430Microglial priming is primarily epigenetic, with metabolic changes acting as coupled consequences or cofactorsKDM6B0.609$0.55SDA-2026-04-07-gap-d
#431Temporal TFEB Modulation TherapyTFEB0.609$0.54SDA-2026-04-03-gap-d
#432The Glial Ketone Metabolic Shunt HypothesisHMGCS20.608$0.55SDA-2026-04-02-gap-v
#433Correcting Gut Microbial Dopamine Imbalance to Support Systemic Dopaminergic FunctionDDC0.606$0.52SDA-2026-04-01-gap-2
#434Circadian-Gated Ketone Window HypothesisOXCT10.606$0.57SDA-2026-04-03-gap-d
#435TREM2-Mediated Microglial Checkpoint TherapyTREM20.606$0.54SDA-2026-04-03-gap-s
#436HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM TransitionHK20.605$0.61SDA-2026-04-16-gap-d
#437TREM2-Microglial Clearance Enhancement as Common Mechanism for Injury PreventionTREM20.604$0.58SDA-2026-04-14-gap-p
#438Selective TFEB Cofactor EnhancementTFE30.602$0.54SDA-2026-04-03-gap-d
#439NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for Reverse SenescenceSIRT10.602$0.56SDA-2026-04-26-gap-p
#440STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Interruption of IFN-I Feedback LoopingTMEM173 (STING)0.601$0.58SDA-2026-04-15-gap-p
#441LRP1-Dependent Tau Uptake DisruptionLRP10.600$0.72SDA-2026-04-04-gap-t
#442TREM2-Dependent Senescent Microglia Disrupt Astrocyte Communication NetworksTREM2/TYROBP0.600$0.55SDA-2026-04-03-gap-a
#443TREM2-Mediated Oligodendrocyte-Microglia Cross-talk in White Matter NeurodegenerationTREM20.600$0.58SDA-2026-04-03-gap-a
#444TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement CascadeTNF; TNFRSF1A; C1R; C1S0.600$0.55SDA-2026-04-08-gap-p
#445mTORC1 Hyperactivation Impairs Autophagic Flux and Drives SenescenceMTOR/TFEB/TFE30.600$0.55SDA-2026-04-06-gap-p
#446C1Q-Mediated Defective Efferocytosis Driving Necrotic Core ExpansionC1QA/C1QC0.600$0.55SDA-2026-04-07-gap-p
#447TREM2-Mediated Astroglial Reactivity in NeurodegenerationTREM20.600$0.57SDA-2026-04-03-gap-a
#448APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex NeurodegenerationAPOE40.600$0.56SDA-2026-04-06-gap-p
#449Oligodendrocyte-Targeted Myelin Sulfatide Restoration TherapyCST, GAL3ST10.599$0.54SDA-2026-04-03-gap-d
#450OPC differentiation blockade contributes to white matter degeneration in early-stage ADPDGFRA0.599$0.55SDA-2026-04-04-analy
#451Metabolic Reprogramming via Coordinated Multi-Gene CRISPR CircuitsPGC1A, SIRT1, FOXO3, mitochondrial biogenesis genes0.599$0.52SDA-2026-04-03-gap-c
#452Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A2 PolarizationAHR, CYP1A1, NFKB1, IL60.597$0.57SDA-2026-04-14-gap-p
#453Glycosaminoglycan Template Disruption ApproachHSPG20.597$0.53SDA-2026-04-01-gap-9
#454Selective C1q-CRP vs. C1q-IgG Axis InhibitionC1QA/C1QB/C1QC, CRP, FCGR1A0.597$0.57SDA-2026-04-16-gap-p
#455Brain Insulin Resistance with Glucose Transporter DysfunctionGLUT3/GLUT40.596$0.55SDA-2026-04-02-gap-v
#456Netrin-1 Gradient RestorationNTN10.595$0.54sda-2026-04-01-gap-0
#457VCP-Mediated Autophagy EnhancementVCP0.595$0.64SDA-2026-04-04-gap-t
#458NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement AmplificationNAMPT, SIRT10.592$0.57SDA-2026-04-16-gap-2
#459TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse LossTREM2,C1Q0.591$0.56SDA-2026-04-16-gap-p
#460Neuronal MHC Class I Expression as a Selectivity DeterminantH2-Kb (H2-K1), Lilrb4 (LilrB2)0.591$0.56SDA-2026-04-07-gap-p
#461Multiplexed Base Editing for Simultaneous Neuroprotective Gene ActivationSOD1, TARDBP, BDNF, GDNF, IGF-10.590$0.54SDA-2026-04-03-gap-c
#462Microglial Replacement and Ontogeny ShiftCCR20.590$0.56SDA-2026-04-07-gap-d
#463TREM2-Mediated Microglial Dysfunction Disrupts Oligodendrocyte Tau Clearance NetworksTREM20.589$0.56SDA-2026-04-03-26abc
#464Cardiovascular-Neuroinflammation Crosstalk InterruptionIL1B, TNFA, NLRP30.587$0.56SDA-2026-04-04-gap-2
#465TREM2-Mediated Oligodendrocyte-Microglia Signaling in White Matter NeurodegenerationTREM20.587$0.56SDA-2026-04-03-gap-a
#466TNFRSF25-Mediated Aging Exosome Pathway InhibitionTNFRSF250.587$0.54SDA-2026-04-03-gap-a
#467TREM2 Signaling Bifurcation with Independent TYROBP-Independent Homeostatic MaintenanceTREM20.586$0.56SDA-2026-04-14-gap-p
#468Senescence-Tau Decoupling TherapyCDKN2A0.585$0.54SDA-2026-04-03-gap-a
#469Mitochondrial-Lysosomal Coupling EnhancerLAMTOR10.585$0.54SDA-2026-04-03-gap-d
#470P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and neurovascular unit dysfunctionP2RY120.585$0.55SDA-2026-04-07-gap-p
#471FcRn Transport Bypass StrategyLDLR0.585$0.52SDA-2026-04-12-gap-d
#472APOE4 Creates Accelerated, Compressed Reversibility WindowAPOE/TREM2 axis, APOE-TREM2 physical interaction0.584$0.54SDA-2026-04-06-gap-d
#473TREM2-Mediated Selective Aggregate Clearance PathwayTREM20.584$0.52SDA-2026-04-01-gap-9
#474IGFBPL1-Mediated Homeostatic RestorationIGFBPL10.584$0.56SDA-2026-04-04-gap-2
#475Gamma Entrainment Synergy: HBOT-Enhanced Cerebral Perfusion Amplifies SST Interneuron-Targeted Neuromodulation-0.583$0.54SDA-2026-04-26-gap-p
#476Extracellular Vesicle Biogenesis ModulationCHMP4B0.582$0.58SDA-2026-04-04-gap-t
#477ITGAM/CD11b direct binding explains microglial phagocytosis blockadeITGAM0.582$0.55SDA-2026-04-21-gap-d
#478CSF1R Inhibition-Mediated Microglial Replacement as a State Transition ResetCSF1R0.581$0.57SDA-2026-04-16-gap-d
#479Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 SignalingNLRP3, LRP1, IL1B, TNF0.580$0.54SDA-2026-04-07-gap-p
#480H7: Dual-Target Strategy (Senolytics + APOE4→3 Conversion)APOE; CDKN2A0.580$0.55SDA-2026-04-06-gap-d
#481H5: Complement Dysregulation Drives Synapse Loss via Senescent APOE4 AstrocytesC3; C3AR1; C5AR10.580$0.55SDA-2026-04-06-gap-d
#482Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement BiosynthesisNFKB1; IKBKB; C1QA; C30.580$0.55SDA-2026-04-08-gap-p
#483αvβ3 Integrin-FAK-SYK-CARD9/NF-κB PathwayITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD90.580$0.55SDA-2026-04-06-gap-p
#484Astrocyte cGAS/STING Activation Converts Protective into Destructive NeuroinflammationSTING (TMEM173) in astrocytes (GFAP+ cells)0.580$0.55SDA-2026-04-07-gap-p
#485TREM2-Driven Phagocytic Receptor Cascades Determine Mitochondrial Antigen Presentation vs. Intracellular MitophagyTREM20.580$0.55SDA-2026-04-08-gap-p
#486AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic NeurodegenerationAQP4; STAT3; MMP90.580$0.55SDA-2026-04-07-gap-p
#487Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Through Attenuated ChemotaxisP2RY120.580$0.55SDA-2026-04-06-gap-p
#488APOE4 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$0.55SDA-2026-04-04-gap-a
#489LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and downstream NLRP3 activationLAMP2 (LGMN)0.580$0.55SDA-2026-04-04-gap-l
#490Complement-Mediated Synaptic ProtectionC1QA0.580$0.54SDA-2026-04-04-gap-2
#491IGFBPL1-Mediated Microglial ReprogrammingIGFBPL10.579$0.54SDA-2026-04-04-gap-2
#492TREM2-Astrocyte Communication in Microglial DysfunctionTREM20.579$0.56SDA-2026-04-03-gap-a
#493Spatial Transcriptome-Guided Precision Cell TherapySOX10 and DLX1/20.578$0.54SDA-2026-04-03-gap-s
#494Synaptic Vesicle Tau Capture InhibitionSNAP250.578$0.59SDA-2026-04-04-gap-t
#495Dynamic Microglial Phenotype Switching Biomarker Panel for Neuroinflammatory Treatment StratificationTREM20.577$0.56SDA-2026-04-16-gap-p
#496TREM2 Promoter Silencing via DNA HypermethylationTREM20.576$0.55SDA-2026-04-07-gap-d
#497HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.575$0.74SDA-2026-04-04-gap-t
#498TREM2-Senescence Cascade in Astrocyte-Microglia Communication BreakdownTREM20.574$0.56SDA-2026-04-03-gap-a
#499Closed-loop transcranial focused ultrasound with 40Hz gamma entrainment to restore hippocampal-cortical connectivity in early MCIPVALB0.573$0.55SDA-2026-04-03-26abc
#500TREM2-P2RY12 Balance Restoration TherapyTREM20.571$0.55SDA-2026-04-04-gap-2
#501Disease-Associated Microglia (DAM) Program Drives IBA1 DownregulationTREM2/TYROBP0.571$0.54SDA-2026-04-07-gap-p
#502PINK1/PARK2-Mediated Mitophagy Enhancement for Neuroinflammation ControlPINK10.571$0.55SDA-2026-04-03-gap-i
#503Neuronal Subtype-Specific Alpha-Synuclein Expression NormalizationSNCA0.571$0.55SDA-BIOMNI-BINDER_D-
#504Direct NF-κB Transcriptional Regulation of C1q Genes in MicrogliaRELA; C1QA/C1QB/C1QC0.570$0.55SDA-2026-04-08-gap-p
#505CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estrogen Receptor-alpha Suppression of NLRP3ESR10.570$0.55SDA-2026-04-06-gap-p
#506Brain-Ester Prodrug Strategy for CNS-Selective HDAC6 InhibitionHDAC6 (class IIb histone deacetylase)0.570$0.55SDA-2026-04-08-gap-d
#507Blocking Astrocyte-Mediated Tau Re-Spreading via Cx43 Hemichannel InhibitionGJA1 (Connexin-43)0.570$0.54SDA-2026-04-04-gap-t
#508TREM2-Dependent Microglial Surveillance Controls AQP4-Mediated Tau Clearance Through Astrocytic Endfoot MaintenanceTREM20.569$0.56SDA-2026-04-03-26abc
#509Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated AmplificationMAPT0.568$0.55SDA-2026-04-03-26abc
#510Tau-Independent Microtubule Stabilization via MAP6 EnhancementMAP60.567$0.56sda-2026-04-01-gap-0
#511NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP AmplificationNLRP30.566$0.54SDA-2026-04-12-gap-d
#512Astroglial Gap Junction Coordination via Connexin-43 Phosphorylation ModulationGJA10.566$0.58sda-2026-04-01-gap-v
#513CX43 hemichannel engineering enables size-selective mitochondrial transferGJA10.566$0.55sda-2026-04-01-gap-v
#514HIF1A stabilization lowers the activation threshold of circadian-disrupted microgliaHIF1A0.566$0.55SDA-2026-04-07-gap-d
#515Vascular-Glial Interface RestorationCLDN50.566$0.54SDA-2026-04-03-gap-s
#516NLRP3 Inflammasome Chromatin Priming Through H3K27ac AccumulationNLRP30.566$0.55SDA-2026-04-07-gap-d
#517Temporal Gating of Microglial ResponsesCLOCK, ARNTL0.565$0.54SDA-2026-04-04-gap-2
#518GluN2B-Mediated Microglial Activation and Tau PropagationGRIN2B0.565$0.51SDA-2026-04-03-26abc
#519Ketone-Primed Thalamocortical Enhancement of Glymphatic Tau ClearanceGRIN2B0.565$0.51SDA-2026-04-03-26abc
#520Closed-loop tACS targeting EC-II somatostatin interneurons to restore dendritic integration and prevent tau-mediated HCN channel dysfunction in ADSST0.564$0.53SDA-2026-04-03-26abc
#521Closed-loop transcranial focused ultrasound targeting entorhinal PV interneurons to restore AnkyrinG-dependent AIS integrity and hippocampal gamma synchrony in Alzheimer's diseasePVALB0.564$0.53SDA-2026-04-03-26abc
#522Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymphatic-mediated amyloid clearance and secondary PV interneuron disinhibition in Alzheimer's diseaseAQP40.564$0.53SDA-2026-04-03-26abc
#523Timed 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
#524P2X7R PET Imaging for NLRP3 Inflammasome-Associated PrimingP2RX7/NLRP30.563$0.54SDA-2026-04-06-gap-d
#525Fractalkine Axis Amplification via CX3CR1 Positive Allosteric ModulatorsCX3CR10.563$0.53sda-2026-04-01-gap-v
#526Complement C1q Suppression as Mechanism Linking Exercise Plasma to PV Interneuron ProtectionC1QA0.560$0.56SDA-2026-04-14-gap-p
#527MOG-IgG induces spinal cord demyelination through Fcγ receptor-dependent macrophage activationMOG, FCGR1A, FCGR3A, FCGR2A, SYK, IRAK40.560$0.54SDA-2026-04-08-gap-p
#528AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metabolic Coupling DisruptionAQP4; SLC16A1 (MCT1); SLC16A3 (MCT4)0.560$0.54SDA-2026-04-07-gap-p
#529Persistent γH2AX+53BP1 Foci with DREAM Complex Activation Defines Irreversibly Arrested MicrogliaH2AFX (γH2AX), TP53BP1, DREAM complex (LIN9, LIN37, RBL2, E2F4)0.560$0.54SDA-2026-04-06-gap-d
#530Temporal cGAS-STING Activation Stage-Specific Therapeutic TargetingSTING (TMEM173)0.560$0.54SDA-2026-04-07-gap-p
#531Circadian-Gated Maresin Biosynthesis AmplificationALOX120.557$0.56sda-2026-04-01-gap-0
#532Gut-Brain Axis Microbiome ModulationGPR43, GPR109A0.557$0.54SDA-2026-04-04-gap-2
#533Test: TREM2 enhances amyloid clearanceTREM20.555$0.55test-hypothesis-fixt
#534CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microglial Senescence ReversalCYP46A10.555$0.56SDA-2026-04-26-trem2
#535Inhibitory Neuron-Selective WNT Signaling RestorationWNT3A, CTNNB1, TCF7L20.554$0.53SDA-2026-04-03-gap-d
#536Profilin-1 Cytoskeletal Checkpoint EnhancementPFN10.554$0.53SDA-2026-04-03-gap-a
#537Dual NF-κB/MMP Inhibition StrategyNFKB10.554$0.55SDA-2026-04-16-gap-b
#538P2RX7-Mediated Exosome Secretion BlockadeP2RX70.552$0.57SDA-2026-04-04-gap-t
#539Liquid-Liquid Phase Separation Modifier TherapyG3BP10.551$0.53SDA-2026-04-01-gap-9
#540Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional ControlSPP10.551$0.56SDA-2026-04-15-gap-p
#541Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation WindowsNLRP30.551$0.56SDA-2026-04-15-gap-p
#542Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via astrocytic calcium signaling and potassium buffering in Alzheimer's diseaseAQP40.551$0.55SDA-2026-04-03-26abc
#543Oligodendrocyte DNA Repair EnhancementPARP10.550$0.52SDA-2026-04-03-gap-s
#544Digital Twin-Guided Metabolic ReprogrammingPPARGC1A/PRKAA10.550$0.54sda-2026-04-01-gap-0
#545H2: SASP Neutralization via JAK/STAT Inhibition Preserves Astrocyte FunctionIL6R; JAK1; STAT30.550$0.54SDA-2026-04-06-gap-d
#546Surface Exposure of SENP1-β1 Integrin Complex Enables Targeted Senolytic EliminationSENP1, ITGB1 (β1 integrin), ITGAM (CD11b)0.550$0.53SDA-2026-04-06-gap-d
#547Combined NAMPT-Alectinib Targeting of SASP-Complement CascadeNAMPT, SIRT1, C1QA/C1QB/C1QC, IL1B0.549$0.55SDA-2026-04-16-gap-p
#548Miro1-Mediated Mitochondrial Trafficking Enhancement TherapyRHOT10.549$0.51SDA-2026-04-01-gap-2
#549YWHAG-Mediated TFEB Subcellular TargetingYWHAG0.549$0.53SDA-2026-04-03-gap-d
#550Perinatal Hypoxia-Primed Microglia TargetingHIF1A, NFKB10.548$0.53SDA-2026-04-04-gap-2
#551SYK-Independent TREM2 Pathways Remain Functional in TYROBP DeficiencySYK, TREM20.548$0.54SDA-2026-04-14-gap-p
#552Microglial TREM2-Independent Pathway ActivationDAP12, SYK, PLCG20.547$0.52SDA-2026-04-03-gap-d
#553CD300f Immune Checkpoint ActivationCD300F0.545$0.53SDA-2026-04-03-gap-a
#554Epigenetic Memory Reprogramming via CRISPRa-Mediated Chromatin RemodelingSIRT1, FOXO3, NRF2, TFAM0.544$0.53SDA-2026-04-03-gap-c
#555Trans-Synaptic Adhesion Molecule ModulationNLGN10.544$0.53SDA-2026-04-04-gap-t
#556HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding InhibitorDNAJB60.544$0.51SDA-2026-04-01-gap-9
#557Temporal Decoupling via Circadian Clock ResetCLOCK0.543$0.58sda-2026-04-01-gap-0
#558TREM2-GluN2B Circuit: Microglial Control of Thalamocortical Oscillations and Glymphatic Tau ClearanceTREM20.543$0.55SDA-2026-04-03-26abc
#559Cerebrospinal Fluid p-tau217-Guided Astrocyte-Derived Extracellular Vesicle Delivery of lncRNA-0021 in Early-Stage ADCSF p-tau217 (biomarker), lncRNA-0021, astrocyte-derived extracellular vesicles0.542$0.56SDA-2026-04-26-gap-p
#560Astrocyte Metabolic Memory ReprogrammingSIRT10.541$0.53SDA-2026-04-04-gap-d
#561Test: TREM2 enhances amyloid clearanceTREM20.541$0.47test-hypothesis-fixt
#562Test: TREM2 enhances amyloid clearanceTREM20.541$0.47test-hypothesis-fixt
#563Test: TREM2 enhances amyloid clearanceTREM20.541$0.47test-hypothesis-fixt
#564Test: TREM2 enhances amyloid clearanceTREM20.541$0.48test-hypothesis-fixt
#565Test: TREM2 enhances amyloid clearanceTREM20.541$0.47test-hypothesis-fixt
#566H6: Epigenetic Reset via APOE4→APOE3 Conversion Reverses SenescenceAPOE; HDAC1; EZH20.540$0.53SDA-2026-04-06-gap-d
#567TAM Receptor (MERTK/AXL) Cross-RegulationMERTK, AXL, TYRO3, PROS1 (Protein S), GAS60.540$0.53SDA-2026-04-06-gap-p
#568H5: Olfactory System as a Toxicant Funnel into Layer IINLRP3, CX3CR1, TLR40.540$0.53SDA-2026-04-02-gap-e
#569Systemic IL-6–STAT3–Hepatic C3 Axis and BBB-Mediated Complement TranslocationIL6; STAT3; C30.540$0.53SDA-2026-04-08-gap-p
#570Soluble 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
#571P2Y6R activation by UDP from damaged neurons drives microglial phagocytosis and exosomal re-secretion in mid-to-late diseaseP2RY60.540$0.53SDA-2026-04-07-gap-d
#572Dual-Phase Medium-Chain Triglyceride InterventionHMGCS2/CPT1A0.540$0.52SDA-2026-04-04-gap-d
#573Microglial Exosome-Mediated Tau PropagationMAPT0.539$0.54SDA-2026-04-03-26abc
#574Lysosomal Membrane Repair EnhancementCHMP2B0.538$0.56sda-2026-04-01-gap-0
#575ABCA7-TREM2 Co-Targeting for Microglial Lipid HandlingABCA7 + TREM2 (combinatorial)0.538$0.53SDA-2026-04-14-gap-p
#576Glymphatic System-Enhanced Antibody Clearance ReversalAQP40.537$0.58sda-2026-04-01-gap-0
#577Test: TREM2 enhances amyloid clearanceTREM20.537$0.56test-hypothesis-fixt
#578CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering NF-κB-Dependent SPP1 TranscriptionSPP10.535$0.60SDA-2026-04-06-gap-p
#579NFκB/C1Q SASP Modulation for Synaptic ProtectionC1Q0.534$0.53SDA-2026-04-26-gap-p
#580Blood-Brain Barrier SPM Shuttle SystemTFRC0.533$0.57sda-2026-04-01-gap-0
#581Gut Barrier Permeability-α-Synuclein Axis ModulationCLDN1, OCLN, ZO1, MLCK0.533$0.53SDA-2026-04-01-gap-2
#582Lactate/Pyruvate Ratio Dynamics in CSF as a Neuroinflammation-Metabolism Interface BiomarkerLDHA, TREM20.532$0.56SDA-2026-04-04-SDA-2
#583PLCG2 Allosteric Modulation as a Precision Therapeutic for TREM2-Dependent Microglial DysfunctionPLCG20.532$0.54SDA-2026-04-01-gap-0
#584EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.532$0.53sda-2026-04-12-ev-ad
#585Mitochondrial-Cytokine Axis ModulationMitochondrial respiratory complexes and inflammatory cytokine receptors0.532$0.52SDA-2026-04-03-gap-a
#586Cryptic Exon Silencing RestorationTARDBP0.531$0.55sda-2026-04-01-gap-v
#587Modulating Tunneling Nanotube (TNT) Formation via M-Sec/Noradrenaline SignalingTNFRSF12A (M-Sec)0.530$0.53SDA-2026-04-04-gap-t
#588C1Q-Angiogenic Axis Promoting Plaque NeovascularizationC1QA/C1QC0.530$0.53SDA-2026-04-07-gap-p
#589Therapeutic Repurposing: C1-INH as Plaque-Stabilizing AgentC1R/C1S0.530$0.53SDA-2026-04-07-gap-p
#590CX3CR1-Targeted AntimiR-155 Oligonucleotides for Microglial Priming ReversalMIR155 (microRNA-155)0.530$0.53SDA-2026-04-08-gap-d
#591Astrocytic Lactate Shuttle Enhancement for Grid Cell BioenergeticsSLC16A20.529$0.55sda-2026-04-01-gap-0
#592PINK1/Parkin-Independent Mitophagy Bypass for Enhanced Donor MitochondriaBNIP3/BNIP3L0.529$0.51SDA-2026-04-01-gap-2
#593Lipid Nanoparticle Encapsulation of IGFBPL1-mRNAIGFBPL10.527$0.53SDA-2026-04-06-gap-d
#594TREM2 Epigenetic Window for Microglial Lipid MetabolismTREM2/HDAC10.525$0.53SDA-2026-04-07-gap-d
#595Pharmacogenomic CNS Drug Optimization PlatformCYP450 enzymes, transporters, and drug targets0.524$0.53SDA-2026-04-04-gap-d
#596TREM2-Dependent Microglial Control of Thalamocortical-Glymphatic Tau ClearanceTREM20.524$0.53SDA-2026-04-03-26abc
#597Circadian Clock Epigenetic Desynchronization WindowBMAL1/HDAC30.524$0.53SDA-2026-04-07-gap-d
#598C1q Binding to Specific Synaptic Proteomes via Neurexin/Neuroligin ComplexesNRXN1, NLGN1 (Neuroligin 1)0.522$0.52SDA-2026-04-07-gap-p
#599TREM2 Agonism to Redirect Microglia from Synaptic Pruning to OPTN-Deficient Neuron ProtectionTREM20.521$0.53SDA-2026-04-14-gap-p
#600Restoring AQP4 Astrocyte Polarization Enhances Glymphatic Tau Clearance and Limits Template-Dependent SpreadingAQP40.520$0.52SDA-2026-04-04-gap-2
#601Dysregulated microglial glycolysis via HIF1α activation shifts the balance from neuroprotective surveillance to complement-mediated synapse engulfmentHIF1A, LDHA, LDHB, PKM2, TREM2, AMPK/mTOR0.520$0.53SDA-2026-04-02-gap-s
#602Telomere Attrition and DNA Damage Response Activation Induces Microglial SenescenceTP53/CDKN2A/CDKN1A/ATM/ATR0.520$0.53SDA-2026-04-06-gap-p
#603Loss of Nuclear Lamin B1 Distinguishes Senescent Microglia from Inflammatory ActivationLMNB1 (Lamin B1)0.520$0.53SDA-2026-04-06-gap-d
#604GATA4 Stabilization and NF-κB Co-activation Identifies Senescent MicrogliaGATA4, SQSTM1/p62, NFKB subunits0.520$0.53SDA-2026-04-06-gap-d
#605M-Sec/TNTA2-mediated tunneling nanotube formation drives glia-neuron tau propagation in mid-stagesTNFAIP20.520$0.53SDA-2026-04-07-gap-d
#606Mitochondrial DNA Damage and cGAS-STING Activation Induces Microglial SenescenceCGAS/STING1/TMEM1730.520$0.53SDA-2026-04-06-gap-p
#607Severely Depleted mtDNA and Impaired OXPHOS Defines Senescent MicrogliaMT-ND1, MT-CO1, TFAM, SIRT30.520$0.53SDA-2026-04-06-gap-d
#608TSPO PET Kinetic Modeling for Priming State DiscriminationTSPO0.520$0.51SDA-2026-04-06-gap-d
#609Piezoelectric Nanochannel BBB DisruptionCLDN5, OCLN0.519$0.53sda-2026-04-01-gap-0
#610NRF2 Activation to Counteract Oxidative Stress from RGS6 Deficiency-0.518$0.51SDA-2026-04-17-gap-p
#611Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Downregulation via NRF2NRF2/NFE2L20.517$0.53SDA-2026-04-07-gap-p
#612Hippocampus ages transcriptionally faster than cerebellum, defining a regional vulnerability axis conserved across speciesCLU0.516$0.53aging-mouse-brain-20
#613Vocal Cord Neuroplasticity StimulationCHR2/BDNF0.515$0.54sda-2026-04-01-gap-0
#614EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.513$0.60sda-2026-04-12-ev-ad
#615GAS6/TAM Axis Activation Stabilizes Blood-Brain Barrier to Reduce Neuroinflammatory Cell Infiltration in Alzheimer's DiseaseGAS6/TAM receptor complex0.513$0.53SDA-2026-04-14-gap-p
#616Test: TREM2 enhances amyloid clearanceTREM20.512$0.53test-hypothesis-fixt
#617Microbial Metabolite-Mediated α-Synuclein DisaggregationSNCA, HSPA1A, DNMT10.511$0.52SDA-2026-04-01-gap-2
#618Tripartite Synapse Cell Type-Nonautonomous Crosstalk: Coordinated FailureC1Q0.510$0.52SDA-2026-04-02-gap-s
#619Primed microglia occupy a hybrid high-glycolysis and high-respiration metabolic statePDHA10.510$0.52SDA-2026-04-07-gap-d
#620Blood Monocyte Epigenetic Signature as Surrogate for Microglial PrimingEpigenetic landscape (TLR4, NLRP3, IL1B regulatory regions)0.509$0.51SDA-2026-04-06-gap-d
#621Circulating IBA1 Protein Absorption/Interference with DetectionAIF1/IBA10.507$0.53SDA-2026-04-07-gap-p
#622Epigenetic Dysregulation of APOE Microglial ExpressionAPOE0.507$0.51SDA-2026-04-07-gap-d
#623PKM2 nuclear translocation bridges metabolism and inflammatory transcription in primed microgliaPKM20.506$0.52SDA-2026-04-07-gap-d
#624TYRO3-STAT1 Axis to Preserve Parvalbumin Interneuron Function by Suppressing IL-1β-Mediated Inflammatory DamageTYRO30.506$0.53SDA-2026-04-14-gap-p
#625Synthetic Biology Approach: Designer Mitochondrial Export SystemsSynthetic fusion proteins0.505$0.51SDA-2026-04-01-gap-2
#626Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late InhibitionSPP10.503$0.51SDA-2026-04-07-gap-p
#627APOE4 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$0.52SDA-2026-04-04-gap-a
#628NETosis Amplification by C1Q in Plaque NeutrophilsC1QA/C1QC0.500$0.51SDA-2026-04-07-gap-p
#629Early Postnatal TGF-beta Signaling Establishes Lifelong Regional Vulnerability Through Irreversible Transcriptional ImprintingTGFBR10.500$0.52SDA-2026-04-06-gap-p
#630Selectively Inhibit Maladaptive AQP4-Driven Astrocyte-Microglia Inflammatory Signaling in Parkinsonian InjuryAQP4, NFKB1, IL1B, TNF0.500$0.52SDA-2026-04-07-gap-p
#631SIRT1-Mediated Epigenetic Restoration of MFSD2A Expression Re-enables SPM Precursor Transport in Aged BBBMFSD2A / SIRT1 (deacetylase activator axis)0.500$0.51SDA-2026-04-12-gap-d
#632Alectinib-C1q Complex Hijacks TREM2's Synaptic Protective Binding InterfaceC1QA/C1QB/C1QC, TREM20.500$0.53SDA-2026-04-16-gap-p
#633TREM2-Mediated Microglial Dysfunction Drives Tau-Induced Blood-Brain Barrier BreakdownTREM20.499$0.53SDA-2026-04-03-26abc
#634Conditional CRISPR Kill Switches for Aberrant Protein ClearanceUBE3A, PARK2, PINK10.496$0.60SDA-2026-04-03-gap-c
#635TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated Survival and Metabolic SignalingSPP10.496$0.51SDA-2026-04-06-gap-p
#636Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critical Neuroinflammatory WindowsNLRP30.496$0.52SDA-2026-04-15-gap-p
#637TREM2-Mediated Microglial Metabolic Reprogramming Accelerates Tau Pathological SpreadTREM20.494$0.53SDA-2026-04-03-26abc
#638YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Perivascular FibroblastsSPP10.492$0.59SDA-2026-04-06-gap-p
#639GluN2B-Regulated Microglial Phagocytosis of Tau Aggregates via CX3CR1 SignalingGRIN2B0.491$0.52SDA-2026-04-03-26abc
#640P2RY12/P2RY13 Purinergic Receptor Metabolic RewiringP2RY12, P2RY13, CTNNB1 (β-catenin), GSK3β0.490$0.51SDA-2026-04-06-gap-p
#641Testosterone-Derived DHT Amplifies Microglial Androgen Receptor Signaling Driving Male-Biased NeuroinflammationAR0.490$0.51SDA-2026-04-06-gap-p
#642C1q-Mediated Delivery of miR-33 Antisense Oligonucleotides for Enhanced APOE4 LipidationmiR-33a/miR-33b0.489$0.51SDA-2026-04-16-gap-d
#643APOE4 Structural Remodeling via HSP70 Chaperone Enhancement StrategyHSP70/APOE40.486$0.51SDA-2026-04-16-gap-d
#644Oligodendrocyte Progenitor Cell Metabolic ReprogrammingPDK1, PFKFB3, LDHA0.486$0.57SDA-2026-04-03-gap-d
#645GluN2B-Mediated Perivascular Pericyte Control of Glymphatic Tau ClearanceGRIN2B0.485$0.52SDA-2026-04-03-26abc
#646TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inflammasome RegulationTFEB0.485$0.50SDA-2026-04-03-gap-i
#647PINK1/PARK2-LC3 Mitophagy EnhancementPINK10.485$0.50SDA-2026-04-03-gap-i
#648SIRT3 gates microglial surveillance versus primed metabolism through mitochondrial deacetylationSIRT30.482$0.50SDA-2026-04-07-gap-d
#649Microglia-Derived Extracellular Vesicle Engineering for Targeted Mitochondrial DeliveryRAB27A/LAMP2B0.482$0.47SDA-2026-04-01-gap-2
#650ISG Threshold Model Explains Acute vs Chronic Neurodegeneration OutcomesUSP18 / JAK/STAT pathway0.480$0.51SDA-2026-04-07-gap-p
#651Enteric Nervous System Prion-Like Propagation BlockadeTLR4, SNCA0.480$0.48SDA-2026-04-01-gap-2
#652CX3CR1 PET with Nano-bodies for Microglial Surveillance State MappingCX3CR10.477$0.50SDA-2026-04-06-gap-d
#653Optogenetic Control of Mitochondrial Transfer NetworksChR20.476$0.47SDA-2026-04-01-gap-2
#654Ferroptosis as Context-Dependent and Motor Neuron-Subtype Selective-0.475$0.52SDA-2026-04-18-gap-d
#655CD44-Mediated Src/PI3K/Akt Signaling CascadeCD44, SRC, PI3K p85 (PIK3R1), MTOR0.470$0.50SDA-2026-04-06-gap-p
#656C1Q-Glia Cross-Talk in Vascular Dementia PathogenesisC1QA/C1QC0.470$0.50SDA-2026-04-07-gap-p
#657Prohibitin-2 Mitochondrial Cross-Seeding Hub DisruptionPHB20.469$0.46SDA-2026-04-01-gap-9
#658APOE and TREM2 interact to modulate age-dependent microglial dysfunctionTREM20.467$0.53aging-mouse-brain-20
#659Cross-Tissue Communication DisruptionMULTIPLE0.466$0.51SDA-2026-04-16-gap-b
#660RNA-Binding Competition Therapy for TDP-43 Cross-SeedingTARDBP0.465$0.45SDA-2026-04-01-gap-9
#661TYROBP Network Hyperactivation Marks Point of No ReturnTYROBP/SYK axis, MAPK/ERK signaling0.463$0.49SDA-2026-04-06-gap-d
#662Microglial Priming Window for HDAC1-Dependent DAM TransitionHDAC10.463$0.50SDA-2026-04-07-gap-d
#663Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology into NeuroinflammationMLKL / RIPK10.460$0.50SDA-2026-04-07-gap-p
#664TSPO-Mediated TDP-43 Mitochondrial ImportTSPO (TSPO), TDP-43-TSPO protein-protein interaction0.460$0.50SDA-2026-04-07-gap-p
#665Selective Microglial Senescence Targeting via TREM2 ModulationTREM20.459$0.52SDA-2026-04-04-gap-s
#666Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional ControlSPP10.459$0.00SDA-2026-04-15-gap-p
#667Intranasal IGFBPL1 Delivery via Olfactory PathwayIGFBPL10.459$0.49SDA-2026-04-06-gap-d
#668Kinase Inhibitor-C1q Structural Convergence for Bifunctional Drug DesignC1QA/C1QB/C1QC, ALK, SYK0.458$0.54SDA-2026-04-16-gap-p
#669CSF Neurofilament Light Chain-Guided Astrocyte-Derived Extracellular Vesicle Delivery of lncRNA-0021 in ADCSF neurofilament light chain (NfL), lncRNA-0021, astrocyte-derived extracellular vesicles0.458$0.52SDA-2026-04-26-gap-p
#670C1q Inhibition Prevents Synaptic Mitochondrial Dysfunction via Microglial-Neuronal Cross-Talk NormalizationC1QA/C1QB/C1QC0.455$0.49SDA-2026-04-15-gap-p
#671Mitochondrial Damage-Triggered SPP1 Inflammasome CouplingSPP10.453$0.50SDA-2026-04-15-gap-p
#672TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic ClearanceTREM2 (Triggering receptor expressed on myeloid cells 2) + SYK (spleen tyrosine kinase)0.453$0.51SDA-2026-04-13-gap-p
#673Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal ExpressionMFGE8, NPTX2 (Neuronal Pentraxin 1)0.451$0.49SDA-2026-04-07-gap-p
#674α4β1 Integrin (VLA-4) and JAK/STAT PathwayITGA4, ITGB1 (α4β1 heterodimer), JAK1/JAK2, STAT30.450$0.49SDA-2026-04-06-gap-p
#675Astrocytic APOE4 Disruption of GABAergic Support Increasing Neuronal VulnerabilitySLC1A2 (GLT-1), GABRA1, GABRB3, GAD10.450$0.49SDA-2026-04-07-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$0.49SDA-2026-04-08-gap-p
#677CSF Neurofilament Light-Triggered Astrocyte-Derived Exosome Dosing Maximizes lncRNA-0021 Therapeutic Window in ADCSF neurofilament light (biomarker), lncRNA-0021, astrocyte-derived exosomes0.450$0.51SDA-2026-04-26-gap-p
#678Astrocytic SPP1 Modulation for Neuroinflammatory ResolutionSPP10.447$0.50SDA-2026-04-15-gap-p
#679C1q-Alectinib Complexation Disrupts Tight Junction Integrity to Enable Paracellular Brain PenetrationCLDN5, OCLN0.445$0.49SDA-2026-04-17-gap-d
#680MITF Acts as the Primary Transcriptional Effector Downstream of HDAC1/2 Deletion, Driving the DAM2 Lysosomal Program Through De-repression of Phagocytic EnhancersMITF0.444$0.50SDA-2026-04-13-gap-p
#681Microglial Membrane Camouflage Exploits CD47-SIRPα Checkpoint DisinhibitionCD47, SIRPA, PTPN6, PTPN110.444$0.50SDA-2026-04-16-gap-p
#682RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular FibroblastsSPP10.442$0.49SDA-2026-04-06-gap-p
#683Monocyte Trojan Horse Cell TherapyIGFBPL10.441$0.49SDA-2026-04-06-gap-d
#684Test: TREM2 enhances amyloid clearanceTREM20.437$0.49test-hypothesis-fixt
#685Blood-Brain Barrier Disruption Enabling Peripheral Inflammatory InsultPDGFRB, CLDN5, OCLN, FGB0.430$0.49SDA-2026-04-07-gap-p
#686GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation-0.429$0.47SDA-2026-04-17-gap-p
#687Source-Specific SPP1 Inhibition: Perivascular Cell TargetingSPP1 (perivascular)0.429$0.48SDA-2026-04-07-gap-p
#688Microbiome-Derived Tryptophan Metabolite NeuroprotectionAHR, IL10, TGFB10.427$0.45SDA-2026-04-01-gap-2
#689C1q-Targeted miR-33 ASO Delivery for APOE4 Hyper-Lipidation via Microglial Receptor-Mediated TranscytosismiR-33a/miR-33b0.427$0.48SDA-2026-04-16-gap-d
#690Lactate-HCAR1 signaling maintains a self-reinforcing glycolytic priming loopHCAR10.427$0.48SDA-2026-04-07-gap-d
#691C1q-Conjugated miR-33 ASO Brain Delivery for Enhanced APOE4 LipidationmiR-33a/miR-33b0.423$0.48SDA-2026-04-16-gap-d
#692P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription via Calcineurin/NFAT PathwaySPP10.423$0.56SDA-2026-04-06-gap-p
#693Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic VulnerabilityC1QA, C3, C3AR1 (complement cascade)0.419$0.50SDA-2026-04-13-gap-p
#694P2RY12-mediated cerebral VSMC dysfunction establishes a vicious cycle with microglial P2RY12 activationP2RY12 (dual: VSMC + microglia)0.418$0.49SDA-2026-04-07-gap-p
#695HDAC2-Specific Repression of PU.1 Pioneer Factor Target Sites Suppresses the IL-33/ST2-Phagocytic Axis; HDAC2 Deletion Specifically Unmasks These EnhancersHDAC20.415$0.51SDA-2026-04-13-gap-p
#696C1q-Alectinib Complexation Enhances CNS Penetration via Microglial C1qR-Mediated Uptake and RedistributionC1QBP0.415$0.49SDA-2026-04-17-gap-d
#697Test: TREM2 enhances amyloid clearanceTREM20.400$0.47test-hypothesis-fixt
#698LncRNA-HDAC1 Complex Formation Locks Microglia in Primed StateHDAC1/NEAT10.400$0.48SDA-2026-04-07-gap-d
#699IGFBPL1 Peptide Mimetics for Drug-Like BBB PermeabilityIGFBPL10.397$0.51SDA-2026-04-06-gap-d
#700CSF1R Inhibition Reversal Window Depends on Microglia Replacement KineticsCSF1R, nestin+ progenitor pool0.395$0.47SDA-2026-04-06-gap-d
#701BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic primingARNTL0.389$0.47SDA-2026-04-07-gap-d
#702Bacterial Enzyme-Mediated Dopamine Precursor SynthesisTH, AADC0.384$0.44SDA-2026-04-01-gap-2
#703LRP1-Autophagy BBB Permeabilization for Antibody TransportLRP1; ATG7; OPTN (autophagy pathway); CLDN5 (tight junctions)0.380$0.47SDA-2026-04-02-gap-b
#704P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via SASP secretionP2RY120.373$0.47SDA-2026-04-07-gap-p
#705Ferroptosis as Epiphenomenon of Terminal Collapse-0.363$0.47SDA-2026-04-18-gap-d
#706Age-related neuroinflammation mimics early Alzheimer's disease pathologyGFAP0.362$0.53aging-mouse-brain-20
#707Gap Junction Hemichannel Modulation for Controlled Mitochondrial ExchangePANX10.361$0.44SDA-2026-04-01-gap-2
#708Ferroptosis as Primary Driver of Motor Neuron Death-0.339$0.46SDA-2026-04-18-gap-d
#709CHMP2B vs. CHMP2A Subunit Targeting Creates a Therapeutic Window in ESCRT-Dependent Tau SortingCHMP2B, CHMP2A, CHMP4B0.330$0.45SDA-2026-04-06-gap-d
#710Novel Hypothesis on Metabolic Dysregulation in NeurodegenerationSLC16A1 (MCT1)0.330$0.39-
#711Partial Agonist/SPP1 Splice Variant Strategy: Splice-Switching TherapeuticsSPP1 splicing factors0.311$0.45SDA-2026-04-07-gap-p
#712[Archived Hypothesis]-0.300$0.30legacy-pre-pipeline-
#713[Archived Hypothesis]-0.300$0.30legacy-pre-pipeline-
#714C1q-Alectinib Complexation Facilitates Brain Penetration via Receptor-Mediated TranscytosisC1Q0.161$0.42SDA-2026-04-17-gap-d
#715Direct C1q Binding Enables FcγR-Independent Complement Activation on Tumor CellsC1Q0.148$0.42SDA-2026-04-17-gap-d
#716Human Serum Albumin-Mediated Displacement Creates False-Positive C1q Binding SignalsC1Q0.132$0.41SDA-2026-04-17-gap-d
#717C1q Binding Reflects Broader Kinase Inhibitor Promiscuity Rather Than Specific Complement TargetingC1Q0.124$0.42SDA-2026-04-17-gap-d
#718Alectinib Binds Mitochondrial C1q-like Proteins (C1QDC1) Rather Than Circulating C1qC1Q0.122$0.42SDA-2026-04-17-gap-d
#719C1q Binding Analysis Across ALK Inhibitor Chemical Series Would Resolve SpecificityC1Q0.115$0.43SDA-2026-04-17-gap-d
#720P2RX7-PANX1 Channel Blockade for Neuroinflammatory Cascade Interruption-0.105$0.42SDA-NEUROINFLAM-BIOM
#721TREM2 Agonism with CX3CR1 Antagonism for Microglial HomeostasisTREM20.105$0.41SDA-NEUROINFLAM-BIOM
#722CD300f Immunoglobulin Receptor as Neuroinflammatory Brake-0.105$0.42SDA-NEUROINFLAM-BIOM
#723IL-33/ST2 Axis Augmentation for Synaptic Protection-0.105$0.42SDA-NEUROINFLAM-BIOM
#724NLRP3 Inflammasome Suppression via Selective Caspase-1 Inhibition-0.105$0.40SDA-NEUROINFLAM-BIOM
#725TYROBP Causal Network Inhibition for Microglial Repolarization-0.105$0.42SDA-NEUROINFLAM-BIOM
#726Alectinib's Putative C1q Binding Derives from Hydrophobic Aggregation Rather Than Direct Protein-Protein InteractionC1Q0.105$0.44SDA-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