| h-2901c57778 | Critical Period Hypothesis: The Therapeutic Window Closes When Neuronal Homeosta | 0.64 | 0.65 | NfL, p-tau217, p-tau231, ATF4, TOMM40 | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062052-7bcf4b6c |
| h-0c9e2166ed | Small Molecule Modulation of Phase Separation | 0.64 | 0.60 | FUS, TDP-43, G3BP1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041428-53b81741 |
| h_seaad_002 | Heterogeneous astrocyte activation states differentially impact neuronal surviva | 0.64 | 0.78 | GFAP | promoted | 2026-04-04 | SDA-2026-04-04-analysis_sea_ad_001 |
| h-d4f71a6b | Transglutaminase-2 Cross-Linking Inhibition Strategy | 0.64 | 0.60 | TGM2 | proposed | 2026-04-03 | SDA-2026-04-01-gap-9137255b |
| h-3da804f5 | Mitochondrial NAD+ Salvage Enhancement | 0.64 | 0.50 | STING1 | proposed | 2026-04-04 | SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402 |
| h-10b5bf6f | Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelo | 0.64 | 0.40 | SOD1, HTT, TARDBP | proposed | 2026-04-04 | SDA-2026-04-03-gap-crispr-neurodegeneration-20260402 |
| h-0f2b2111 | Selective Neuronal Vulnerability Network Targeting | 0.64 | 0.65 | Cell-type specific vulnerability markers | proposed | 2026-04-04 | SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402 |
| h-trem2-3374766c | Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in Early Amyloid Phase | 0.64 | 0.72 | TREM2 | promoted | 2026-04-05 | SDA-2026-04-02-gap-001 |
| h-da6fee1910 | H1: CK2 Hyperphosphorylation Locks G3BP1 in Hyper-condensed State | 0.64 | 0.62 | CSNK2A1/CSNK2B, G3BP1 | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-041428-4c4414ad |
| hyp_test_c4cd97c6 | Test: TREM2 enhances amyloid clearance | 0.64 | 0.27 | TREM2 | proposed | 2026-04-17 | test-hypothesis-fixtures-v1 |
| h-d8f2bbc9 | Astrocyte Metabolic Reprogramming via APOE4 Correction | 0.64 | 0.70 | APOE | promoted | 2026-04-04 | SDA-2026-04-03-gap-seaad-v2-20260402032945 |
| h-a735b8480c | Layer-Specific Excitatory Neuron Vulnerability in Temporal Cortex | 0.64 | 0.65 | EIF2AK3 | proposed | 2026-04-28 | SDA-2026-04-28-gap-methodol-20260427-041425-9e73b245 |
| h-a2662cf8d8 | ER-Mitochondria Calcium Microdomains Couple Mitophagy and ER-Phagy Initiation | 0.64 | 0.65 | ITPR1 (IP3R1), VDAC1, MCU | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062132-e71b3ef7 |
| h-dca86efa | TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection Filter | 0.64 | 0.62 | TREM2 | proposed | 2026-04-16 | SDA-2026-04-15-gap-debate-20260410-112730-24052bbe |
| h-a620b95b | CX3CL1-CX3CR1 Mimetic Therapy for Neuroprotection | 0.64 | 0.62 | CX3CL1-CX3CR1 Mimetic | proposed | 2026-04-26 | SDA-2026-04-17-gap-microglial-subtypes-pharmaco-202604170000 |
| SDA-2026-04-02-gap-t | HSP90-Tau Disaggregation Complex Enhancement | 0.63 | 0.46 | HSP90AA1 | proposed | 2026-04-17 | SDA-2026-04-04-gap-tau-prop-20260402003221 |
| h-917f37cf | DLK MAPK Pathway Inhibition to Block Tau-Induced Neurotoxicity Without Directly | 0.63 | 0.55 | MAP2K7/MAP3K12 | promoted | 2026-04-16 | SDA-2026-04-15-gap-pubmed-20260410-100455-ff18091d |
| h-analogy-e866a41f | Gamma entrainment therapy to restore motor cortical inhibitory-excitatory balanc | 0.63 | 0.55 | PVALB | active | 2026-04-28 | |
| h-analogy-38e863ca | Closed-loop optogenetic targeting of PV interneurons to restore motor circuit in | 0.63 | 0.55 | | active | 2026-04-28 | |
| h-analogy-410d3197 | Closed-loop transcranial focused ultrasound targeting motor cortex SST interneur | 0.63 | 0.55 | SST | active | 2026-04-28 | |
| h-analogy-9377cede | TBK1 Insufficiency in Alzheimer Microglia Drives a Senescence-Like Inflammatory | 0.63 | 0.55 | TBK1 (or upstream regulator TREM2 as indirect proxy) | active | 2026-04-28 | |
| h-bf78d35ce1 | Thalamic Reticular Nucleus (TRN) GluN2B Hyperexcitability Disrupts AQP4 Polariza | 0.63 | 0.60 | GRIN2B (TRN neurons); AQP4 polarization via SNTA1 | proposed | 2026-04-28 | SRB-2026-04-28-h-var-e2b5a7e7db |
| h-246051ec90 | Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1 | 0.63 | 0.58 | STAT3/JAK1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041439-306c2cdb |
| h-f4e38f4d53 | G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autoph | 0.63 | 0.52 | G3BP1 | proposed | 2026-04-21 | SDA-2026-04-08-gap-pubmed-20260406-041423-9c2c2ee3 |
| h-b2aeabb1 | Palmitoylethanolamide-Based Endocannabinoid Therapy | 0.63 | 0.43 | PPARA | proposed | 2026-04-16 | SDA-2026-04-16-gap-bbb-tjp-20260416041707 |
| h_seaad_003 | Layer V excitatory neurons show selectively enhanced vulnerability through dysre | 0.63 | 0.75 | SLC17A7 | promoted | 2026-04-04 | SDA-2026-04-04-analysis_sea_ad_001 |
| h-6eb5dfe99b | Chaperone-Degradation Coupling Prevents Aggregate Persistence by Shunting Seeds | 0.63 | 0.68 | STUB1 (CHIP), UPS pathway | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062052-28cbc764 |
| h-trem2-8df94363 | TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk Allele | 0.63 | 0.70 | TREM2 | promoted | 2026-04-05 | SDA-2026-04-02-gap-001 |
| h-2531ed61 | Disease-Associated Microglia Metabolic Reprogramming | 0.63 | 0.70 | TREM2 | promoted | 2026-04-12 | SDA-2026-04-03-gap-seaad-v4-20260402065846 |
| h-1ac3dd5b75 | C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macrophages | 0.63 | 0.65 | C1QA/C1QC | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062122-b65f8ebc |
| h-fd52a7a0 | FOXO3-Longevity Pathway Epigenetic Reprogramming | 0.63 | 0.40 | FOXO3 | debated | 2026-04-02 | sda-2026-04-01-gap-v2-bc5f270e |
| h-8d124bccfe | Enteric Nervous System Dysfunction as Self-Reinforcing Pathological Loop | 0.63 | 0.65 | SNCA/GFAP/VIP/nNOS/CHAT | proposed | 2026-04-26 | SDA-2026-04-26-gut-brain-pd-ffdff6f4 |
| h-a3a1a15a56 | Butyrate-Producing Commensal Depletion Creates Vicious Cycle: HDAC3 Overactivity | 0.63 | 0.72 | HDAC3, TREM2, PGC-1α, NLRP3, HIF1α | proposed | 2026-04-26 | SDA-2026-04-26-gap-20260425-225305 |
| h-348264d348 | Pericyte senescence is sufficient to weaken the BBB even without classic amyloid | 0.63 | 0.61 | CDKN2A, CDKN1A, IL6, CXCL8, TGFB1 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-de5dfc4391 |
| h-ff7cdd9b05 | APOE4-microglial complement signaling causes cholinergic-enriched synaptic vulne | 0.63 | 0.67 | APOE, C1QA, C1QB, C1QC, C3, ITGAM | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-e849205bca |
| h-0ca883fab0 | C1q has spatially distinct functions, with synapse-bound C1q primarily nucleatin | 0.63 | 0.64 | C1QA,C1QB,C1QC,C4A,C4B,C3,ITGAM,ITGB2,LAIR1 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-afba1a80bd |
| h-1e980cc6cb | Intestinal Permeability Defects → Systemic LPS Translocation → Microglial Primin | 0.63 | 0.68 | Tight junction complex (CLDN1, OCLN, TJP1), LBP, CD14, TLR4, | proposed | 2026-04-22 | sda-2026-04-01-gap-20260401-225155 |
| h-aa33319bb9 | Autophagosome-Lysosome Fusion Defects as Primary Driver of α-Synuclein Propagati | 0.63 | 0.75 | VPS41, STX17, HOPS complex, TRPML1 (MCOLN1) | proposed | 2026-04-22 | SDA-2026-04-02-gap-2026-04-01-gap-006 |
| h-658e41c70e | CX3CR1 Agonism Enhances Microglial Phagocytosis of Extracellular Tau Seeds, Prev | 0.63 | 0.68 | CX3CR1 | proposed | 2026-04-22 | SDA-2026-04-04-gap-20260404-052358 |
| h-319955cb66 | Targeting Synaptic Vesicle Release Machinery to Block Tau Exocytosis | 0.63 | 0.65 | SNAP25 | proposed | 2026-04-22 | SDA-2026-04-04-gap-tau-prion-spreading |
| h-652a706ec8 | Restoration of V-ATPase function reverses lysosomal acidification defect in AD n | 0.63 | 0.68 | ATP6V1A, ATP6V0C | proposed | 2026-04-22 | SDA-2026-04-04-gap-lysosomal-cathepsin-ad |
| h-4a83434d37 | Epigenetic Bivalency at CDKN2A Locus Distinguishes Senescent from Activated Micr | 0.63 | 0.72 | CDKN2A, H3K9me3, DREAM complex (LIN9, LIN37, RBL2) | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062101-6af4ba5f |
| h-d44394f958 | Steric Occlusion of G3BP1 Oligomerization Interface | 0.63 | 0.68 | G3BP1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041423-2d1db50c |
| h-7eea3c3380 | Treat Glymphatic Failure by Coupling AQP4-Targeted Therapy to Sleep/Noradrenergi | 0.63 | 0.58 | AQP4, ADRA2, LC | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041445-7e1dc0b2 |
| h-c883a9eb10 | Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoot Repair in NMOSD | 0.63 | 0.60 | AQP4, IL6R, CD19, C5 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041445-7e1dc0b2 |
| h-815e1cb9c9 | Hierarchical Phase Separation with Scaffold Cores | 0.63 | 0.62 | Ddx6, 4E-T, FMRP, TIA1, G3BP1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041428-53b81741 |
| h-05b40151e8 | Partial OSK Reprogramming Reverses Epigenetic Aging Without Dedifferentiation | 0.63 | 0.75 | Oct4; Sox2; Klf4; TP53 | proposed | 2026-04-21 | SDA-2026-04-10-gap-20260410-091440 |
| h-9d22b570 | Programmable Neuronal Circuit Repair via Epigenetic CRISPR | 0.63 | 0.30 | NURR1, PITX3, neuronal identity transcription factors | proposed | 2026-04-03 | SDA-2026-04-03-gap-crispr-neurodegeneration-20260402 |
| h-0d576989 | Selective Cholinergic Protection via APP Pathway Modulation | 0.63 | 0.65 | APP | proposed | 2026-04-04 | SDA-BIOMNI-CLINICAL-b7a71edd |
| SDA-2026-04-16-hyp-9 | APOE4-Driven Astrocyte Senescence as Primary Target | 0.63 | 0.46 | APOE,CDKN1A,BCL2L1 | proposed | 2026-04-16 | SDA-2026-04-04-gap-senescent-clearance-neuro |