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Hypotheses

Top-ranked hypotheses by composite score. Filter by lifecycle status, disease, or target gene; sort by score or recency. Click a row to open evidence, scoring detail, and any live prediction markets referencing it.

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#HypothesisTarget geneStatusCompositeUpdated
1Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration
neurodegeneration mechanistic 37 ev
h-var-08a4d5c07a
NLRP3, CASP1, IL1B, PYCARDvalidated0.9242026-05-13Open →
2APOE-Dependent Autophagy Restoration
neurodegeneration therapeutic 42 ev
h-51e7234f
MTORvalidated0.8952026-05-16Open →
3p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43…
neurodegeneration combination 16 ev
h-ccc05373
MAPK14/PRMT1validated0.8952026-05-16Open →
4SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence
neurodegeneration mechanistic 55 ev
h-var-b7de826706
SIRT1validated0.8932026-05-16Open →
5TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration
neurodegeneration mechanistic 53 ev
h-var-66156774e7
TREM2validated0.8922026-05-16Open →
6TREM2-APOE Axis Dissociation for Selective DAM Activation
neurodegeneration 14 ev
h-5b378bd3
TREM2-APOE axisvalidated0.8862026-05-13Open →
7Circadian Glymphatic Entrainment via Targeted Orexin Receptor Modulation
neurodegeneration therapeutic 29 ev
h-9e9fee95
HCRTR1/HCRTR2validated0.8822026-05-13Open →
8Senescent Cell ASM-Complement Cascade Intervention
neurodegeneration therapeutic 43 ev
h-var-76afa28dfc
SMPD1validated0.8522026-05-16Open →
9Prime Editing Precision Correction of APOE4 to APOE3 in Microglia
neurodegeneration mechanistic 30 ev
h-42f50a4a
APOEvalidated0.8502026-05-16Open →
10Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in Neurodegenerat…
neurodegeneration therapeutic 37 ev
h-var-e81fbd3868
SMPD3validated0.8442026-05-16Open →
11TYROBP (DAP12) Conditional Antagonism for Early-Stage Neuroprotection
neurodegeneration 18 ev
h-f503b337
TYROBPvalidated0.8442026-05-13Open →
12AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue respo…
neurodegeneration therapeutic 31 ev
h-43f72e21
PRKAA1validated0.8332026-05-16Open →
13Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neur…
neurodegeneration mechanistic 31 ev
h-var-a0933e666d
AIM2, CASP1, IL1B, PYCARD, TARDBPvalidated0.8242026-05-16Open →
14SASP-Mediated Complement Cascade Amplification
neurodegeneration mechanistic 30 ev
h-58e4635a
C1Q/C3validated0.8222026-05-16Open →
15Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates…
neurodegeneration mechanistic 31 ev
h-var-adfecef68a
NLRP3, CASP1, IL1B, PYCARDvalidated0.8222026-05-13Open →
16HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase…
neurodegeneration combination 19 ev
h-ff0d545d
HSPB1validated0.8202026-05-14Open →
17Extracellular Vesicle Biogenesis Modulation
neurodegeneration therapeutic 11 ev
SDA-2026-04-02-gap-tau-prop-20260402003221-H003
CHMP4Bvalidated0.8142026-05-16Open →
18CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerabili…
neurodegeneration combination 20 ev
h-0bcda2e0
APOE, CLUvalidated0.8112026-05-13Open →
19LRP1-Dependent Tau Uptake Disruption
neurodegeneration therapeutic 12 ev
SDA-2026-04-02-gap-tau-prop-20260402003221-H001
LRP1validated0.8082026-05-16Open →
20CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion
neurodegeneration 14 ev
h-0cbe9bac
CSF1R-TREM2validated0.8082026-05-16Open →
21Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to Neur…
neurodegeneration therapeutic 11 ev
h-5b35f7a5
HCAR2validated0.8082026-05-13Open →
22Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration
neurodegeneration mechanistic 31 ev
h-var-6957745fea
AIM2, CASP1, IL1B, PYCARDvalidated0.8052026-05-13Open →
23Targeted Butyrate Supplementation for Microglial Phenotype Modulation
neurodegeneration therapeutic 22 ev
h-3d545f4e
GPR109Apromoted0.8052026-05-16Open →
24Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for…
neurodegeneration mechanistic 31 ev
h-var-af9eb8e59b
AIM2, CASP1, IL1B, PYCARD, PPIFvalidated0.8042026-05-13Open →
25TREM2-mTOR Co-Agonism for Metabolic Reprogramming
neurodegeneration 13 ev
h-2e03f316
TREM2-mTOR pathwayvalidated0.8032026-05-13Open →
26Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neurodegeneration
neurodegeneration mechanistic 31 ev
h-var-d04a952932
AIM2, CASP1, IL1B, PYCARDvalidated0.8032026-05-13Open →
27Microglial TREM2-SYK Pathway Enhancement
neurodegeneration therapeutic 8 ev
h-48858e2a
TREM2promoted0.7982026-05-14Open →
28Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)
neurodegeneration mechanistic 77 ev
h-11795af0
APOEpromoted0.7952026-05-13Open →
29Targeting SASP-Complement Amplification Through HIF-1α Downstream Effectors
neurodegeneration mechanistic 10 ev
h-a9f2570b
C1QA, C1QB, C3, IL1Bpromoted0.7932026-05-14Open →
30Senescent Microglia Resolution via Maresins-Senolytics Combination
neurodegeneration therapeutic 27 ev
h-3f02f222
BCL2L1debated0.7912026-05-16Open →
31Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory Priming
neurodegeneration therapeutic 49 ev
h-f3fb3b91
TLR4proposed0.7892026-05-13Open →
32VCP-Mediated Autophagy Enhancement
neurodegeneration therapeutic 19 ev
SDA-2026-04-02-gap-tau-prop-20260402003221-H004
VCPproposed0.7872026-05-16Open →
33Competitive APOE4 Domain Stabilization Peptides
neurodegeneration mechanistic 73 ev
h-d0a564e8
APOEpromoted0.7842026-05-13Open →
34Integrated Biomarker Panel for Therapeutic Window Identification
neurodegeneration combination 21 ev
h-ecd9ed6c
CHI3L1promoted0.7842026-05-13Open →
35SASP-Driven Aquaporin-4 Dysregulation
neurodegeneration mechanistic 30 ev
h-807d7a82
AQP4promoted0.7822026-05-13Open →
36Selective Acid Sphingomyelinase Modulation Therapy
neurodegeneration therapeutic 36 ev
h-de0d4364
SMPD1promoted0.7822026-05-16Open →
37TREM2-mediated microglial tau clearance enhancement
neurodegeneration combination 15 ev
SDA-2026-04-02-gap-tau-prop-20260402003221-H002
TREM2proposed0.7802026-05-16Open →
38TFEB Nuclear Translocation to Reset Lysosomal-Hypoxia Axis
neurodegeneration mechanistic 21 ev
h-810ec0eb
TFEB, MTORpromoted0.7792026-05-14Open →
39Selective HDAC3 Inhibition with Cognitive Enhancement
neurodegeneration therapeutic 42 ev
h-0e675a41
HDAC3promoted0.7792026-05-16Open →
40SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Micro…
neurodegeneration 11 ev
h-26b9f3e7
SIRT1, PGC-1α (PPARGC1A), NAMPTpromoted0.7782026-05-13Open →
41Transcriptional Autophagy-Lysosome Coupling
neurodegeneration mechanistic 50 ev
h-ae1b2beb
FOXO1promoted0.7772026-05-16Open →
42CX3CR1-TREM2 Integration for Synapse Pruning Normalization
neurodegeneration 15 ev
h-7597968b
CX3CR1-TREM2proposed0.7762026-05-16Open →
43Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation
neurodegeneration therapeutic 35 ev
h-23a3cc07
FCGRTpromoted0.7732026-05-16Open →
44Chromatin Accessibility Restoration via BRD4 Modulation
neurodegeneration therapeutic 45 ev
h-addc0a61
BRD4promoted0.7682026-05-16Open →
45CYP46A1 Overexpression Gene Therapy
neurodegeneration therapeutic 38 ev
h-2600483e
CYP46A1promoted0.7682026-05-16Open →
46HDL/apoE Particle Remodeling as a Therapeutic Switch for CAA Prevention
neurodegeneration therapeutic 20 ev
h-ed8dee29
ABCA1proposed0.7662026-05-14Open →
47APOE4 Allosteric Rescue via Small Molecule Chaperones
neurodegeneration mechanistic 55 ev
h-44195347
APOEdebated0.7652026-05-13Open →
48Chromatin Remodeling-Mediated Nutrient Sensing Restoration
neurodegeneration mechanistic 43 ev
h-var-a09491064e
SMARCA4promoted0.7642026-05-16Open →
49SASP-Mediated Cholinergic Synapse Disruption
neurodegeneration mechanistic 32 ev
h-1acdd55e
MMP2/MMP9promoted0.7632026-05-13Open →
50Circadian Clock-Autophagy Synchronization
neurodegeneration mechanistic 32 ev
h-b7898b79
CLOCKdebated0.7632026-05-13Open →
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Hypothesis index sorted by composite score. Each hypothesis is a scientific claim produced by multi-agent analysis, scored on 10 dimensions. Filter by hypothesis_type, target_gene, disease, or status. Links to /hypotheses/[id] for the full scoring breakdown.

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