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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.

107
total hypotheses
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#HypothesisTarget geneStatusCompositeUpdated
1Closed-loop transcranial focused ultrasound with gamma entrainment to restore h…
Alzheimer's disease therapeutic 65 ev
h-var-cedb86877e
PVALBpromoted—2026-05-16Open →
2Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscill…
Alzheimer's disease therapeutic 65 ev
h-var-bf1195d1ee
SSTpromoted—2026-05-16Open →
3Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to…
Alzheimer's disease therapeutic 50 ev
h-var-b7e4505525
SSTvalidated0.9682026-05-16Open →
4Closed-loop optogenetic targeting PV interneurons to restore theta-gamma coupli…
Alzheimer's disease therapeutic 52 ev
h-var-e95d2d1d86
PVALBvalidated0.9592026-05-16Open →
5Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to…
Alzheimer's disease therapeutic 50 ev
h-var-f110ef2e0a
SSTproposed0.9552026-05-16Open →
6Gamma entrainment therapy to restore hippocampal-cortical synchrony
Alzheimer's disease therapeutic 51 ev
h-bdbd2120
SSTvalidated0.9462026-05-16Open →
7Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscill…
Alzheimer's disease therapeutic 50 ev
h-var-a4975bdd96
CCKvalidated0.9122026-05-16Open →
8Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation sta…
Alzheimer's disease therapeutic 72 ev
h-var-9c0368bb70
BDNFvalidated0.8852026-05-16Open →
9Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling…
Alzheimer's disease therapeutic 51 ev
h-var-e47f17ca3b
SSTvalidated0.8842026-05-16Open →
10Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhyt…
Alzheimer's disease therapeutic 51 ev
h-var-4eca108177
PVALBvalidated0.8692026-05-16Open →
11Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscill…
Alzheimer's disease therapeutic 65 ev
h-var-6612521a02
PVALBvalidated0.8652026-05-16Open →
12Optogenetic restoration of hippocampal gamma oscillations via selective PV inte…
Alzheimer's disease therapeutic 57 ev
h-var-6c90f2e594
PVALBvalidated0.8652026-05-16Open →
13Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta…
Alzheimer's disease therapeutic 59 ev
h-var-862d6a66d2
PVALBvalidated0.8632026-05-16Open →
14Real-time gamma-guided transcranial focused ultrasound targeting EC-II SST inte…
Alzheimer's disease therapeutic 50 ev
h-var-d33964b962
SSTvalidated0.8272026-05-16Open →
15Gamma entrainment repairs cross-regional phase-amplitude coupling via CA1 Schaf…
Alzheimer's disease 5 ev
h-620a7b5b79
GRIN2A/GRIN2B (NR2A/NR2B NMDA receptors), CAMK2Avalidated0.8262026-05-14Open →
16Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation
Alzheimer's disease therapeutic 71 ev
h-856feb98
BDNFvalidated0.8202026-05-16Open →
17Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and b…
Alzheimer's disease therapeutic 58 ev
h-var-14d7585dd1
PVALBvalidated0.8112026-05-16Open →
18Dual-Receptor Antibody Shuttling
Alzheimer's disease therapeutic 10 ev
h-48d1115a
—validated0.8032026-05-16Open →
19Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with…
Alzheimer's disease therapeutic 50 ev
h-var-ee70969116
PVALBproposed0.7972026-05-16Open →
20Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activ…
Alzheimer's disease therapeutic 58 ev
h-var-d98a992599
SSTproposed0.7842026-05-16Open →
21Gamma entrainment reactivates PV+ interneuron ensembles to restore inhibition/e…
Alzheimer's disease 6 ev
h-ec5db48878
PV+ interneuron populations; GABRA1, GABRA5 (GABA-A α1, α5 subunits); KCNJ9 (Kir3.1)proposed0.7772026-05-14Open →
22APOE4-Specific Proteolytic Fragment Inhibition Therapy
Alzheimer's disease therapeutic 31 ev
h-var-600b3e39aa
APOEproposed0.7772026-05-16Open →
23Prefrontal sensory gating circuit restoration via PV interneuron enhancement
Alzheimer's disease therapeutic 51 ev
h-62f9fc90
PVALBpromoted0.7752026-05-16Open →
24Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical me…
Alzheimer's disease therapeutic 51 ev
h-var-787aa9d1b4
SSTpromoted0.7752026-05-16Open →
25Gamma entrainment induces activity-dependent BDNF release to rescue NMJ and den…
Alzheimer's disease 5 ev
h-b98ff29728
BDNF (brain-derived neurotrophic factor); NTRK2 (TrkB); CREBBP/EP300 (CREB)proposed0.7732026-05-14Open →
26Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscill…
Alzheimer's disease therapeutic 50 ev
h-var-ea70ada256
SSTproposed0.7672026-05-16Open →
27Closed-loop focused ultrasound targeting CA1 PV interneurons to restore theta-g…
Alzheimer's disease therapeutic 50 ev
h-var-7eaceb5a55
PVALBpromoted0.7542026-05-16Open →
28Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and…
Alzheimer's disease therapeutic 55 ev
h-var-3b982ec3d2
SSTpromoted0.7522026-05-16Open →
29Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamm…
Alzheimer's disease therapeutic 50 ev
h-var-55da4f915d
SSTpromoted0.7482026-05-16Open →
30KCNQ2/3 (M-current) Channel Restoration Reactivates Theta Oscillation Dynamics
Alzheimer's disease 5 ev
h-6b1d223140
KCNQ2/KCNQ3proposed0.7252026-05-14Open →
31Gamma entrainment suppresses hippocampal ERK1/2 hyperactivity to decrease AD-re…
Alzheimer's disease 5 ev
h-f7d4cdb947
MAPK3/MAPK1 (ERK1/2); MAP2K1/MAP2K2 (MEK1/2); RASGRF1proposed0.7112026-05-14Open →
32TREM2-APOE4 Axis Drives Metabolic Inflexibility in DAM
Alzheimer's disease mechanistic 9 ev
h-immunity-c64967ab
TREM2, APOE4, LDHAopen0.7082026-05-14Open →
33Gamma entrainment restores astrocyte-neuron metabolic coupling through Cx43 hem…
Alzheimer's disease 5 ev
h-24d53538c7
GJA1 (connexin 43/Cx43); P2RY1 (P2Y1 receptor); SLC16A3 (MCT4 lactate transporter); SRR/DAO (D-serine synthesis)proposed0.7002026-05-14Open →
34ISR/eIF2α~P Overflow Represses Synaptic Protein Synthesis Downstream of Tau/Aβ…
Alzheimer's disease cross_disease_analogy 5 ev
h-analogy-8b267076
EIF2AK3 (PERK)active0.6832026-05-16Open →
35Gamma entrainment enhances TREM2-mediated microglial clearance of Aβ plaques vi…
Alzheimer's disease 6 ev
h-76d375b520
TREM2 (triggering receptor expressed on myeloid cells 2); SYK (spleen tyrosine kinase); CDK5proposed0.6782026-05-14Open →
36Gamma entrainment corrects AD-related clock gene dysregulation to normalize hip…
Alzheimer's disease 5 ev
h-4118a57ecd
PER1/PER2 (circadian clock genes); ARNTL (BMAL1); CREBBP (CREB-S133P); RORA (RORα)proposed0.6762026-05-14Open →
37Adaptive Closed-Loop Gamma/Theta-Gamma Entrainment of Entorhinal-Hippocampal Ci…
Alzheimer's disease 6 ev
h-96aac98502
N/A (electrophysiologic network target)proposed0.6702026-05-14Open →
38C1q-TREM2 Competition for Phosphatidylserine as Pruning Checkpoint
Alzheimer's disease mechanistic 8 ev
h-immunity-c3bc272f
C1QA, C1QB, TREM2, PSRopen0.6692026-05-14Open →
39Vascular mural cell degeneration precedes and exacerbates parenchymal pathology
Alzheimer's disease mechanistic 15 ev
h_seaad_005
PDGFRBproposed0.6612026-05-16Open →
40SPP1+ DAM as Source of Autoimmunity in Neurodegeneration
Alzheimer's disease mechanistic 8 ev
h-immunity-03dc171e
SPP1, GALECTIN3, LGALS3, CXCR4open0.6602026-05-14Open →
41TDP-43 Liquid-Liquid Phase Separation Dominance in Stress Granules Predisposes…
Alzheimer's disease cross_disease_analogy 5 ev
h-analogy-9e00d99e
TARDBPactive0.6502026-05-16Open →
42Calibrated PLCG2 activation can reproduce the protective rs72824905 microglial…
Alzheimer's disease therapeutic_genetics 8 ev
h-gwas-plcg2-protective-mimicry-5dee99f5
PLCG2proposed0.6502026-05-14Open →
43Epigenetic Reprogramming of Microglial Memory
Alzheimer's disease therapeutic 7 ev
h-e5f1182b
DNMT3A, HDAC1/2debated0.6472026-05-16Open →
44Optogenetic PV Cell Activation Restores Gamma Power via PV Protein Upregulation
Alzheimer's disease 5 ev
h-76204e63a4
PVALB/GAD1proposed0.6352026-05-14Open →
45TBK1 Insufficiency in Alzheimer Microglia Drives a Senescence-Like Inflammatory…
Alzheimer's disease cross_disease_analogy 6 ev
h-analogy-9377cede
TBK1 (or upstream regulator TREM2 as indirect proxy)active0.6332026-05-16Open →
46Microglial TREM2 downregulation impairs damage-associated response in late-stag…
Alzheimer's disease mechanistic 22 ev
h_seaad_001
TREM2promoted0.6262026-05-16Open →
47APOE4-Targeted Ultrasonic Lipidation Enhancement for Gamma Oscillation Restorat…
Alzheimer's disease therapeutic 31 ev
h-var-fd2fd0825b
APOE/PVALBproposed0.6252026-05-16Open →
48Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening…
Alzheimer's disease therapeutic 50 ev
h-var-f4b4d4de63
PVALBproposed0.6222026-05-16Open →
49TREM2-ABI3 actin-phagocytosis coupling is a higher-yield AD target than either…
Alzheimer's disease combination_target 8 ev
h-gwas-trem2-abi3-phagocytosis-5dee99f5
TREM2/ABI3proposed0.6202026-05-14Open →
50Synaptic Pruning Precision Therapy
Alzheimer's disease therapeutic 7 ev
h-494861d2
C1QA, C3, CX3CR1, CX3CL1debated0.6122026-05-16Open →
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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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