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Hypotheses

1,886 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
h-3a901ec3Astroglial Gap Junction Coordination via Connexin-43 Phosphorylation Modulation0.720.72GJA1debated2026-04-02sda-2026-04-01-gap-v2-ee5a5023
h-72c719461cC9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD0.720.88C9orf72proposed2026-04-26test-hypothesis-fixtures-v1
h-51302631b4APOE4-driven pericyte injury/senescence is an upstream driver of early BBB break0.720.78APOE4, LRP1, PPIA, MMP9, PDGFRBproposed2026-04-25SDA-2026-04-25-gapdebate-de5dfc4391
h-90b7b77f59Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfolding in Enteric Neuron0.720.72CsgA, CsgB, CsgC, α-synuclein (SNCA)proposed2026-04-22sda-2026-04-01-gap-20260401-225155
h-a5bc82c685Excessive C1q/C3/CR3 complement cascade activation initiates pre-symptomatic syn0.720.72C1QA, C1QB, C1QC, C3, ITGAM/ITGAXproposed2026-04-22SDA-2026-04-02-gap-synaptic-pruning-microglia
h-9ff41c2036H6: Layer II–Specific Loss of NPTX2 and Aberrant AMPAR Trafficking0.720.75NPTX2, ARCproposed2026-04-22SDA-2026-04-02-gap-ec-layer2-vulnerability
h-c410043ac4Antisense Oligonucleotide-Mediated APOE4 Haploinsufficiency0.720.75APOEproposed2026-04-22SDA-2026-04-02-gap-apoe4-targeting
h-a352af801cSASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 Ratio0.720.75CXCL1, CXCL2, MMP3proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-6af4ba5f
h-7af6de6f2aNLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome Phenotype0.720.72NLRP3/CASP1/IL1Bproposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-5f43216e
h-641ea3f1a7H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astrocyte Senescence0.720.72ABCA1/ABCG1; LXR (NR1H3)proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-5d7b9dc0
h-5258e4d0eeAutophagic Receptor Sequestration via K63-Ub 'Signalone' Recognition0.720.25G3BP1proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041423-2d1db50c
h-fca0433042Microglial IFN-β Priming of Motor Neuron cGAS/STING Amplification0.720.70IFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-611cf046
h-d4e73cf08fVCP/p97 ATPase mutations impair extraction of ubiquitinated autophagy substrates0.720.72VCPproposed2026-04-21SDA-2026-04-08-gap-pubmed-20260406-062212-6777e5dd
SDA-2026-04-16-hyp-eMetabolic Reprogramming to Reverse Senescence0.720.79SIRT1,PGC1A,NAMPTpromoted2026-04-16SDA-2026-04-04-gap-senescent-clearance-neuro
h-6756097bASO-Mediated Exon Skipping to Restore FUS-TAZ Chaperone Axis0.720.68FUSpromoted2026-04-15SDA-2026-04-14-gap-pubmed-20260410-184155-2ff305ca
h-97aa8486Stress Granule Phase Separation Modulators0.720.80G3BP1debated2026-04-02sda-2026-04-01-gap-v2-68d9c9c1
h-aa2d317cMagnetosonic-Triggered Transferrin Receptor Clustering0.720.65TFR1debated2026-04-02sda-2026-04-01-gap-008
h-35f04e1bRetinal Vascular Microcirculation Rescue0.720.40PDGFRB/ANGPT1debated2026-04-02sda-2026-04-01-gap-012
h-3a990993Compromised Lysosomal Acidification and Trafficking Due to Neuronal V-ATPase Sub0.720.75ATP6V0/ATP6V1 subunits, ARL8B-SYX17 axisproposed2026-04-26SDA-2026-04-07-gap-pubmed-20260406-062212-ca78691c
h-trem2-f3effd21TREM2-DAP12 Signalosome Enhancement — Boosting PI3K-AKT-mTOR Axis for Microglial0.720.62TREM2, TYROBP, SYK, PI3Kproposed2026-04-05SDA-2026-04-02-gap-001
h-15336069APOE Isoform Conversion Therapy0.720.45APOEproposed2026-04-03sda-2026-04-01-gap-auto-fd6b1635d9
h-b948c32cEngineered Apolipoprotein E4-Neutralizing Shuttle Peptides0.720.30APOE, LRP1, LDLRdebated2026-04-02sda-2026-04-01-gap-008
h-1111ac0598C9orf72 DPRs Impair Autophagy Receptor Docking on Stress Granules0.720.72C9orf72, p62/SQSTM1, OPTNproposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041423-3a6aa4ab
h-25ec762b3fCSF YKL-40 as a Priming-Specific Chitinase Marker0.710.72CHI3L1/YKL-40proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062039-3b945972
h-7e0b5adeCircadian-Synchronized LRP1 Pathway Activation0.710.40LRP1, MTNR1A, MTNR1Bdebated2026-04-02sda-2026-04-01-gap-008
h-trem2-fe8c644aSoluble TREM2 (sTREM2) as Therapeutic Mimic — Decoupling Phagocytosis from Infla0.710.65TREM2, ADAM10, ADAM17proposed2026-04-05SDA-2026-04-02-gap-001
h-1eaa052225Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in A0.710.30TREM2proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-ec89b1e4
h-f373e16bb108EZH2-Mediated H3K27me3 Spreading in Senescent ALS Microglia Silences Neuroprotec0.710.28EZH2 (PRC2) → H3K27me3 silencing of BDNF, GRN, TREM2, MerTKproposed2026-04-26SDA-2026-04-26-gap-20260425215446
h-530326b97069SASP-Secreted MMP-9 from Senescent Microglia Generates Pathological TDP-43 C-Ter0.710.30MMP9 → TARDBP (C-terminal fragments) → cytoplasmic aggregatiproposed2026-04-26SDA-2026-04-26-gap-20260425215446
h-0758b337Purinergic Signaling Polarization Control0.710.70P2RY1 and P2RX7debated2026-04-02sda-2026-04-01-gap-007
h-1f9e65f394Liquid-to-Solid Transition Pathology Reveals Granule Weak Points0.710.82TDP-43, FUS, TIA1, G3BP1debated2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041428-53b81741
h-583535bbGut-BBB Axis: Tributyrin/Butyrate HDAC Inhibition Epigenetically Restores Claudi0.710.74CLDN5proposed2026-04-26SDA-2026-04-26-gap-bbb-permeability-biomarker-20260426
hyp_test_656bc496Test: TREM2 enhances amyloid clearance0.710.33TREM2proposed2026-04-17test-hypothesis-fixtures-v1
h-var-f110ef2e0aClosed-loop transcranial focused ultrasound targeting EC-II SST interneurons to 0.710.65SSTproposed2026-04-07SDA-2026-04-03-26abc5e5f9f2
h-fcd38787TGF-β1–SMAD2/3 Axis as Master Suppressor of Microglial Trained Immunity0.710.78TGFBR1/TGFBR2 → SMAD4 → SMAD2/3proposed2026-04-26SDA-2026-04-08-gap-debate-20260406-062033-ad87c3fb
h-de579cafCircadian Glymphatic Rescue Therapy (Melatonin-focused)0.710.55MTNR1Adebated2026-04-02sda-2026-04-01-gap-v2-18cf98ca
h-9588dd18Early Proteasome Restoration Therapy0.710.75PSMCpromoted2026-04-04SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402
h-4113b0e8Noradrenergic-Tau Propagation Blockade0.710.45ADRA2Adebated2026-04-02sda-2026-04-01-gap-v2-18cf98ca
h-5edc4a7e0558Excess orexin-A worsens AD cognition through wake-driven amyloid production0.710.69HCRTproposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-184240-f72e77ae
h-64d92165APOE4-Specific Microglial Metabolic Rescue0.710.66APOE, ABCA1, LDLRproposed2026-04-04SDA-2026-04-04-gap-neuroinflammation-microglial-20260404
h-a9571dbbHDAC3-Selective Inhibition for Clock Reset0.710.60HDAC3debated2026-04-02sda-2026-04-01-gap-v2-bc5f270e
h-d2d37a81eeaaACSL4 lipid remodeling creates ferroptosis-prone ALS membranes0.710.69ACSL4proposed2026-04-26SDA-2026-04-26-gap-ferroptosis-mnd-768eaeba1be3
h-b9794c8e29Microglial TREM2 Activation Reduces Amyloid-Associated Neurotoxicity0.710.78TREM2proposed2026-04-28SDA-TEST-PREREG-003
h-78c49508e9NRF2 Activation Provides Neuroprotection Across ALS, AD, and PD0.710.72NFE2L2 (NRF2)proposed2026-04-28SDA-TEST-PREREG-003
h-75fd56f128RAB29 Is the Critical Molecular Switch That Determines Whether LRRK2 Signal Ampl0.710.70RAB29proposed2026-04-26SDA-2026-04-23-gap-debate-20260417-033119-54941818
h-4032affe2fMicroglial Disease-Associated States: TREM2-Independent Pathways Driving Neuroin0.710.68APOEproposed2026-04-22SDA-2026-04-02-gap-seaad-debate-v4
h-d9793012deConformational-Selective Blocking of Tau Uptake Reveals Therapeutic Window in Ne0.710.72LRP1, HSPG (SDC3, GPC1), tau conformationsproposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062052-7bcf4b6c
h-82634b359bH4: Senomorphic Compounds Preserve Astrocyte Function While Reversing Senescence0.710.65MTOR; MEGF10; MERTKproposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-5d7b9dc0
h-f9dca82e35Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial Loss0.710.78CCR2proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041439-306c2cdb
h-var-55da4f915dClosed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma0.710.82SSTpromoted2026-04-05SDA-2026-04-03-26abc5e5f9f2
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