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Hypotheses

1,967 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
hyp-SDA-2026-04-12-2Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid Pathology0.790.55CHRNA7 (α7 nicotinic receptor), BACE1debated2026-04-13SDA-2026-04-12-20260411-082446-2c1c9e2d
h-d0a564e8Competitive APOE4 Domain Stabilization Peptides0.780.30APOEpromoted2026-04-02sda-2026-04-01-gap-010
h-ecd9ed6cIntegrated Biomarker Panel for Therapeutic Window Identification0.780.68CHI3L1promoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112330-9abf86eb
h-var-d98a992599Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activa0.780.72SSTproposed2026-04-05SDA-2026-04-03-26abc5e5f9f2
hyp-lyso-snca-1d58cfLAMP2A Liquid-Liquid Phase Separation Defects in Dopaminergic Neurons Create Sel0.780.68LAMP2active2026-04-28
h-01685bc3b9Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)0.780.72CD55 (DAF), CD46 (MCP)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9
h-807d7a82SASP-Driven Aquaporin-4 Dysregulation0.780.70AQP4promoted2026-04-02sda-2026-04-01-gap-013
h-de0d4364Selective Acid Sphingomyelinase Modulation Therapy0.780.80SMPD1promoted2026-04-02SDA-2026-04-01-gap-lipid-rafts-2026-04-01
SDA-2026-04-02-gap-tTREM2-mediated microglial tau clearance enhancement0.780.67TREM2proposed2026-04-17SDA-2026-04-04-gap-tau-prop-20260402003221
h-cross-synth-stressStress-granule RNA-binding protein phase transition across ALS and FTD0.780.74TIA1;HNRNPA1;HNRNPA2B1active2026-04-28SDA-2026-04-28-cross-disease-synthesis
h-9923279defPINK1/Parkin–TREM2 Axis: Convergent Mitophagy Failure Unifies PD (SNCA/αSyn) and0.780.72PINK1,PRKN,TREM2,STUB1,NDUFS7proposed2026-04-28
h-7000ac15c1Therapeutic Window Exists Because Amplified Signals (Not Baseline) Drive Pathoge0.780.78LRRK2proposed2026-04-26SDA-2026-04-23-gap-debate-20260417-033119-54941818
h-dec9f2e970NLRP3 Inhibition (H7): Downstream Inflammatory Reversal0.780.78NLRP3/NLRP3 (NLRP3 inflammasome)proposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-180918-962b1ada-debate
h-17d177c62bSleep-Dependent Glymphatic Clearance Expands the Therapeutic Window by Reducing 0.780.78AQP4, orexin receptor (HCRTR1/2)proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062052-7bcf4b6c
h-810ec0ebTFEB Nuclear Translocation to Reset Lysosomal-Hypoxia Axis0.780.52TFEB, MTORpromoted2026-04-14SDA-2026-04-13-gap-pubmed-20260410-170057-1bea7d88
h-var-f96e38ec20ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlie0.780.82ACSL4superseded2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
h-0e675a41Selective HDAC3 Inhibition with Cognitive Enhancement0.780.80HDAC3promoted2026-04-02SDA-2026-04-04-gap-epigenetic-reprog-b685190e
h-26b9f3e7SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microb0.780.76SIRT1, PGC-1α (PPARGC1A), NAMPTpromoted2026-04-17SDA-BIOMNI-MICROBIO-337ee37a
h-ae1b2bebTranscriptional Autophagy-Lysosome Coupling0.780.71FOXO1promoted2026-04-02sda-2026-04-01-gap-011
h-var-600b3e39aaAPOE4-Specific Proteolytic Fragment Inhibition Therapy0.780.65APOEproposed2026-04-16
h-var-e4cae9d286LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Priming Engine0.780.82LPCAT3debated2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
hyp-lyso-snca-3429d8Exosomal SNCA Propagation from Lysosome-Compromised Neurons Contains a Distinct 0.780.70SNCAactive2026-04-28
h-cross-synth-tbk1-oTBK1-OPTN-p62 selective autophagy failure across ALS, FTD, and PD-like proteotox0.780.73TBK1active2026-04-28SDA-2026-04-28-cross-disease-synthesis
h-7597968bCX3CR1-TREM2 Integration for Synapse Pruning Normalization0.780.52CX3CR1-TREM2proposed2026-04-17SDA-2026-04-01-gap-001
h-var-c56b26facfLPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Substrate Pools in Dise0.780.82LPCAT3debated2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
h-62f9fc90Prefrontal sensory gating circuit restoration via PV interneuron enhancement0.780.75PVALBpromoted2026-04-02SDA-2026-04-03-26abc5e5f9f2
h-var-787aa9d1b4Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical mem0.770.78SSTpromoted2026-04-12SDA-2026-04-03-26abc5e5f9f2
h-028af077miR-33 Antisense Oligonucleotide Hyper-Lipidation Strategy0.770.75miR-33/ABCA1promoted2026-04-16SDA-2026-04-16-gap-debate-20260410-113104-a13caf2e
h-var-8412ce00a4Dual-Circuit Tau Vulnerability Cascade0.770.75MAPTpromoted2026-04-07SDA-2026-04-03-26abc5e5f9f2
h-trem2-f48baa0cTREM2-APOE4 Co-targeting — Simultaneous Correction of Lipid Sensing and Clearanc0.770.67TREM2, APOEproposed2026-04-05SDA-2026-04-02-gap-001
h-6df1bc66Biphasic Ketogenic Intervention Protocol0.770.50HMGCS2proposed2026-04-17SDA-2026-04-03-gap-debate-20260403-222618-2709aad9
h-23a3cc07Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation0.770.30FCGRTpromoted2026-04-02sda-2026-04-01-gap-008
h-c90cca1826Inhibiting Heparan Sulfate Proteoglycan Receptor-Mediated Neuronal Tau Uptake0.770.78SULF1/SULF2proposed2026-04-22SDA-2026-04-04-gap-tau-prion-spreading
h-var-97b18b880dALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE Peroxidat0.770.82ALOX15debated2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
h-c1d5dcbf48TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle Autophagy0.770.78TBK1, OPTN (TBC1D7), NDP52/CALCOCO2proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062132-e71b3ef7
h-89f1963fHypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory Pathway0.770.42GPNMB, CD44proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-170057-a2f72fd8
h-6fe30c39bcSTING Antagonists as ALS Therapeutics: Drug Repurposing0.770.68STING (TMEM173)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-fc60e018
h-c58ac188fcEnhancing Microglial Phagocytosis of Extracellular Tau via TREM2 Activation0.770.82TREM2debated2026-04-22SDA-2026-04-04-gap-tau-prion-spreading
h-eb7e85343bH3: SIRT1 Insufficiency Disconnects Metabolic Sensing from Epigenomic Homeostasi0.770.78SIRT1, NAMPT, NAD+ salvage pathwayproposed2026-04-22SDA-2026-04-04-gap-20260404-120802
h-af0ec8d843Complement C1q-Mediated Synaptic Pruning Drives Early Cognitive Decline in Alzhe0.770.82C1Qproposed2026-04-26legacy-pre-pipeline-import-v1
SDA-2026-04-16-hyp-bOligodendrocyte Precursor Cell Senescence in White Matter Disease0.770.60CSPG4,OLIG2,BCL2proposed2026-04-16SDA-2026-04-04-gap-senescent-clearance-neuro
hyp-SDA-2026-04-12-2Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling0.770.65CHRNA7, CHRM1debated2026-04-13SDA-2026-04-12-20260411-082446-2c1c9e2d
h-addc0a61Chromatin Accessibility Restoration via BRD4 Modulation0.770.60BRD4promoted2026-04-02SDA-2026-04-04-gap-epigenetic-reprog-b685190e
h-2600483eCYP46A1 Overexpression Gene Therapy0.770.85CYP46A1promoted2026-04-02SDA-2026-04-01-gap-lipid-rafts-2026-04-01
h-25580e2eLysosomal Cathepsin-Dependent Tau Clearance0.770.45proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-150544-e3a2eab9
h-var-ea70ada256Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla0.770.78SSTproposed2026-04-12SDA-2026-04-03-26abc5e5f9f2
h-ed8dee29HDL/apoE Particle Remodeling as a Therapeutic Switch for CAA Prevention0.770.62ABCA1proposed2026-04-15SDA-2026-04-15-gap-pubmed-20260411-083043-759b4c5e
h-c49c08c56aKinetic Modeling Predicts Threshold-Dependent Efficacy—Early Intervention Requir0.770.72Seed amplification threshold (RT-QuIC diagnostic)proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062052-28cbc764
h-44195347APOE4 Allosteric Rescue via Small Molecule Chaperones0.760.40APOEdebated2026-04-02sda-2026-04-01-gap-010
h-var-a09491064eChromatin Remodeling-Mediated Nutrient Sensing Restoration0.760.82SMARCA4promoted2026-04-12SDA-2026-04-04-gap-epigenetic-reprog-b685190e
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