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Hypotheses

2,362 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
h-SDA-2026-04-26-gapResidual Vascular Amyloid Prevents Complete CSF p-tau217 Normalization, Requirin0.590.36APOE, CLUproposed2026-04-26SDA-2026-04-26-gap-debate-20260417-033134-20519caa
h-e3a48208Mitochondrial-Lysosomal Coupling Enhancer0.590.50LAMTOR1proposed2026-04-04SDA-2026-04-03-gap-debate-20260403-222617-8eb5bdbc
h-89be8460d0Mitophagy Induction as Neuroprotective Strategy in Sporadic Parkinson's Disease0.580.65USP30proposed2026-04-26legacy-pre-pipeline-import-v1
h-29d142abaaALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding Interfaces0.580.60G3BP1, G3BP2proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041423-3a6aa4ab
h-50d04444e4P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and 0.580.62P2RY12proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041434-d7920f3b
h-9d16afa0FcRn Transport Bypass Strategy0.580.75LDLRproposed2026-04-12SDA-2026-04-12-gap-debate-20260410-112908-13c403ee
h-var-4d43a26612Optogenetic restoration of hippocampal gamma oscillations via selective SST inte0.580.65SSTproposed2026-04-07SDA-2026-04-03-26abc5e5f9f2
h-9025d807PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineur0.580.55PIKFYVE/MCOLN1/PPP3CB/TFEBpromoted2026-04-14SDA-2026-04-13-gap-pubmed-20260410-143119-8ae42941
h-9a721223NOMO1-Mediated Neuronal Resilience Enhancement0.580.45NOMO1proposed2026-04-04SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402
h-85173a30c8APOE4 Creates Accelerated, Compressed Reversibility Window0.580.52APOE/TREM2 axis, APOE-TREM2 physical interactionproposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062045-7a6cf14e
h-3460f820TREM2-Mediated Selective Aggregate Clearance Pathway0.580.50TREM2proposed2026-04-03SDA-2026-04-01-gap-9137255b
h-4e823a876aUpstream restoration of glial lipid efflux and apoE lipidation will outperform d0.580.52LXRproposed2026-04-25SDA-2026-04-25-gapdebate-f4c8357045
h-d4ff5555IGFBPL1-Mediated Homeostatic Restoration0.580.80IGFBPL1debated2026-04-04SDA-2026-04-04-gap-20260404-microglial-priming-early-ad
h-analogy-8485c6fbTREM2-mediated PV interneuron stabilization to restore gamma coherence in protei0.580.45PVALB / TREM2active2026-04-28
h-c0c52aec62Multivalent Scaffold Theory: Rif1 SAF Domain Array as High-Valency Condensate Co0.580.68RIF1proposed2026-04-21SDA-2026-04-10-gap-debate-20260410-075026-23501c3c
h-5240d15b04Pharmacological P2RY12 inhibition (ticagrelor/clopidogrel) as repurposing probe 0.580.58P2RY12proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041434-d7920f3b
h-b35f2ff8Gamma Entrainment Synergy: HBOT-Enhanced Cerebral Perfusion Amplifies SST Intern0.580.52proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-181340-8acb24dc
h-ec79168bGPC4/HSPGs Collaborate with ApoE Isoforms to Dictate Tau Conformational Strain U0.580.58GPC4/APOEpromoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112730-24052bbe
h-d5dc9661b1SCFA Deficiency Disrupts Microglial Homeostasis and Promotes Neurodegeneration0.580.55HDAC3/GPR43 (FFAR2)/IL10/TREM2/OCLNproposed2026-04-26SDA-2026-04-26-gut-brain-pd-ffdff6f4
h-55ef81c5Extracellular Vesicle Biogenesis Modulation0.580.34CHMP4Barchived2026-04-02SDA-2026-04-04-gap-tau-prop-20260402003221
h-56af4a2b91Ganglioside-rich extracellular vesicles preserve alpha-synuclein fibril conforma0.580.54SNCBproposed2026-04-26SDA-2026-04-26-gap-pubmed-20260411-081644-1d2624b8-debate
h-b0defed1ITGAM/CD11b direct binding explains microglial phagocytosis blockade0.580.62ITGAMproposed2026-04-21SDA-2026-04-21-gap-debate-20260417-033037-c43d12c2
h-3685e352CSF1R Inhibition-Mediated Microglial Replacement as a State Transition Reset0.580.70CSF1Rpromoted2026-04-17SDA-2026-04-16-gap-debate-20260410-112642-fffdca96
h-762a78d0afRNA Metabolism and Nucleocytoplasmic Transport Defects0.580.62RanGAP1, NUP205, C9orf72, FUSproposed2026-04-28SDA-2026-04-28-cross-disease-synthesis
h-85bc154b49TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-Lysosome Pathway0.580.62TFEB (MLST8)proposed2026-04-28SDA-TEST-PREREG-003
h-cf3596a8f7Selective c-Abl Inhibition Promotes α-Synuclein Clearance via Autophagy0.580.68ABL1/c-Ablproposed2026-04-26test-hypothesis-fixtures-v1
h-1431a507bfGut Bacterial Metabolite-AhR Dysregulation Converts SCFA-Deficiency into IDO1-Dr0.580.65AHR, IDO1, KYNU, HAAO, GRIN2A, STAT3proposed2026-04-26SDA-2026-04-26-gap-20260425-225305
h-f7db2634eeLXR Agonism (H4): Microglial Lipid Efflux Promotion0.580.62NR1H3 (LXRα/NR1H3)proposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-180918-962b1ada-debate
h-5559a65b3fLiproxstatin-1 as Mechanism-Validation Tool for Ferroptosis Inhibition0.580.65ALOX12/15 (12/15-lipoxygenase) / HDAC4 axisproposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-174000-6451afef-debate
h-c42d677719A lower trazodone dose of 50-100 mg nightly may be sufficient only in dementia p0.580.45HTR2A; HRH1; AQP4proposed2026-04-26
h-ba57f3d3edLYTL and JIP4-dependent lysosomal remodeling may show mutant-selective amplifica0.580.61JIP4,LRRK2,RAB10,RAB35proposed2026-04-25SDA-2026-04-25-gapdebate-9180363b7c
h-16818f9bf1APOE4 Structural Correction by Small Molecule Correctors0.580.55APOE4proposed2026-04-22SDA-2026-04-02-gap-apoe4-targeting
h-d0099a1106Structure-interacting small molecules that stabilize the APOE4 molten globule do0.580.55APOE (protein structure stabilizer)proposed2026-04-22SDA-2026-04-04-gap-apoe4-lipid-metabolism
h-a1f87d1fd6APOE4 drives astrocyte metabolic reprogramming toward glycolysis via PGC-1α supp0.580.58PPARGC1A (PGC-1α), SIRT1, SREBF1 (SREBP1c)proposed2026-04-22SDA-2026-04-04-gap-apoe4-lipid-metabolism
h-e744d98ee1LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and down0.580.55LAMP2 (LGMN)proposed2026-04-22SDA-2026-04-04-gap-lysosomal-cathepsin-ad
h-684a2fffb5Dysregulated G3BP1 Signaling Impairs Local Translation in Neuronal Processes, Co0.580.55G3BP1proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041428-e14e6524
h-d3a2216a86Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Thr0.580.58P2RY12proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-ec89b1e4
h-6358a464acαvβ3 Integrin-FAK-SYK-CARD9/NF-κB Pathway0.580.68ITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD9proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-062118-e3613755
h-0fcf8ff993H5: Complement Dysregulation Drives Synapse Loss via Senescent APOE4 Astrocytes0.580.55C3; C3AR1; C5AR1proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-5d7b9dc0
h-81bb99f5b9H7: Dual-Target Strategy (Senolytics + APOE4→3 Conversion)0.580.58APOE; CDKN2Aproposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-5d7b9dc0
h-3cdc8defe3Limited Calcium Release Without Sufficient Cathepsin Efflux0.580.55TRPML1/MCOLN1, Calcineurin/NFATproposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062150-a6cc7467
h-494ad6afe0Nuclear Export Deficits Increase Cytosolic TDP-43 Burden0.580.55XPO1/CRM1, ALYREF, THOC1/THOC2, TDP-43 NLSproposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-611cf046
h-c1828e7264Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 Signaling0.580.52NLRP3, LRP1, IL1B, TNFproposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062202-c8c5a9a1
h-6f274df61eDisrupted AQP4-Mediated K+ Spatial Buffering Causes Neuronal Hyperexcitability a0.580.58AQP4; KCNJ10 (Kir4.1); ATP1A2proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041445-ce0abc1e
h-47e3c2965cAQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic Neur0.580.55AQP4; STAT3; MMP9proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041445-ce0abc1e
h-9f504f5d4dAstrocyte cGAS/STING Activation Converts Protective into Destructive Neuroinflam0.580.55STING (TMEM173) in astrocytes (GFAP+ cells)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-fc60e018
h-b6af8aa071Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement Biosynthesis0.580.55NFKB1; IKBKB; C1QA; C3proposed2026-04-21SDA-2026-04-08-gap-pubmed-20260406-062128-afe67892
h-6a4c716402TREM2-Driven Phagocytic Receptor Cascades Determine Mitochondrial Antigen Presen0.580.48TREM2proposed2026-04-21SDA-2026-04-08-gap-pubmed-20260406-062132-5d93ddb2
h-07691d28Oxygen Pressure-Dependent BDNF Cascade: DHHC2/PSD95 Stabilization for Synaptic R0.580.64proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-181340-8acb24dc
h-d645402bALOX15 Inhibition Combined with Selenium Augmentation for Synergistic Ferroptosi0.580.58ALOX15, SELENOPproposed2026-04-17SDA-2026-04-16-gap-ferroptosis-als-d2fb6bf796ed
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