| h-b0857ffa5d | cAMP/PKA-Dependent Transcription Factor Activation via Nutrient Stress Sensing | 0.42 | 0.35 | PRKACA, CREB1, CRTC2 | proposed | 2026-04-21 | SDA-2026-04-08-gap-pubmed-20260406-062150-5b7d1556 |
| h-a2b3485737 | Differential Calpain-Mediated Cleavage of Apoptotic vs. Autophagic Substrates | 0.42 | 0.20 | CAPN1/CAPN2 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062150-a6cc7467 |
| h-95fb48b4 | Complement Cascade Activation Bridges Microglial OxPC Sensing to Synaptic Vulner | 0.42 | 0.55 | C1QA, C3, C3AR1 (complement cascade) | proposed | 2026-04-13 | SDA-2026-04-13-gap-pubmed-20260410-165345-41805e1b |
| h-bb7f540f0f | P2RY12-mediated cerebral VSMC dysfunction establishes a vicious cycle with micro | 0.42 | 0.42 | P2RY12 (dual: VSMC + microglia) | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041434-d7920f3b |
| h-SDA-2026-04-26-gap | Neurogranin Co-Normalization Validates p-tau217 as a Surrogate for Synaptic Heal | 0.42 | 0.25 | NRGN, SNAP25 | proposed | 2026-04-26 | SDA-2026-04-26-gap-debate-20260417-033134-20519caa |
| h-var-5effbb1a5e | C1q-Alectinib Complexation Enhances CNS Penetration via Microglial C1qR-Mediated | 0.41 | 0.70 | C1QBP | proposed | 2026-04-21 | SDA-2026-04-17-gap-debate-20260417-033037-c43d12c2 |
| h-b5c803f2 | HDAC2-Specific Repression of PU.1 Pioneer Factor Target Sites Suppresses the IL- | 0.41 | 0.30 | HDAC2 | proposed | 2026-04-13 | SDA-2026-04-13-gap-pubmed-20260410-110327-26e1d6c7 |
| h-79f0c46458 | A-Tract Bulge Conserved Motifs Enable Selective Targeting of NEAT1 Subdomains | 0.41 | 0.35 | NEAT1 | proposed | 2026-04-21 | SDA-2026-04-10-gap-debate-20260410-075007-232fbf62 |
| h-71dd2007 | Oligodendrocyte Precursor Cell Activation to Restore Structural Connectome Integ | 0.41 | 0.35 | Oligodendrocyte Precursor Cell | proposed | 2026-04-25 | SDA-2026-04-16-frontier-connectomics-84acb35a |
| h-1df5ba79 | Bivalent Domain Resolution Failure at Neurodevelopment Genes | 0.41 | 0.50 | Bivalent Domain Resolution | proposed | 2026-04-25 | SDA-2026-04-19-gap-epigenetic-comparative-ad-pd-als |
| h-0f41864d88 | TREM2-independent neuronal protection via cystatin-C/LRP2 signaling | 0.41 | 0.35 | CST3/LRP2/AKT/ERK | proposed | 2026-04-25 | SDA-2026-04-26-gap-pubmed-20260410-150544-e3a2eab9-debate |
| h-eda0cdbe | ITGAX/CD11c Targeting to Eliminate Pro-inflammatory DAM in ALS | 0.41 | 0.48 | ITGAX/CD11c Targeting | proposed | 2026-04-25 | SDA-2026-04-17-gap-microglial-subtypes-pharmaco-202604170000 |
| h-5de005be | PU.1 Degradation via PROTAC for Inflammatory Microglial Polarization | 0.41 | 0.45 | PU.1 Degradation via | proposed | 2026-04-25 | SDA-2026-04-17-gap-microglial-subtypes-pharmaco-202604170000 |
| h-var-85632d5906 | Transferrin-Alectinib Conjugation Enhances Blood-Brain Barrier Transport via Tra | 0.41 | 0.70 | TFRC | proposed | 2026-04-21 | SDA-2026-04-17-gap-debate-20260417-033037-c43d12c2 |
| h-SDA-2026-04-26-gap | MT1 Receptor Activation at Low Doses Synchronizes Suprachiasmatic Nucleus and Re | 0.41 | 0.33 | MTNR1A (MT1), MTNR1B (MT2), PER1/PER2 clock genes, SOD2 | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260411-081101-dfe3eacb |
| h-SDA-2026-04-26-gap | Pulsatile Low-Dose Protocol to Prevent Receptor Desensitization | 0.41 | 0.33 | MT1/MT2 receptors; GRK2/3; β-arrestin | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260411-090734-1be1b913 |
| h-SDA-2026-04-26-gap | Dicer-Processed siRNA-Mediated Transcript Silencing | 0.41 | 0.33 | DICER1 (Dicer); AGO2 (EIF2C2); TNRC6A (GW182) | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260412-094853-199f4f1b |
| h-var-be3485f0c9 | Closed-loop tFUS targeting of EC-II SST interneurons to prevent ACSL4-mediated f | 0.40 | 0.67 | SST | promoted | 2026-04-26 | SDA-2026-04-03-26abc5e5f9f2 |
| h-8114d42b2c | Tau propagation through muscarinic receptor-mediated BBB transcytosis | 0.40 | 0.34 | CHRM1; CHRM3; LRP1 | proposed | 2026-04-29 | SDA-2026-04-29-gap-test-20260425-224949 |
| h-6efe763e0c | HCN1 Channel Normalization for Grid Cell Restoration (Deprioritize) | 0.40 | 0.40 | HCN1 (HCN1) | proposed | 2026-04-28 | SRB-2026-04-28-h-var-b7e4505525 |
| h-8e4e15dc | Branched-Chain Amino Acid Transamination Inhibition to Modulate Neurotransmitter | 0.40 | 0.40 | BCAT1/BCAT2 | proposed | 2026-04-25 | SDA-2026-04-16-frontier-metabolomics-f03b09d9 |
| h-6677933cd7 | Small-Molecule Modulation of G3BP1 Condensate Dynamics via PRMT1 Methylation as | 0.40 | 0.42 | G3BP1, PRMT1 | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-041428-e14e6524 |
| h-aa4f4f07f6 | Cathepsin-Dependent Processing of Pro-Drug Enzymes | 0.40 | 0.40 | CTSD, Unknown substrate X | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062150-a6cc7467 |
| hyp_test_f15ab6d9 | Test: TREM2 enhances amyloid clearance | 0.40 | 0.30 | TREM2 | archived | 2026-04-04 | test-hypothesis-fixtures-v1 |
| h-fa52cd0645 | LncRNA-HDAC1 Complex Formation Locks Microglia in Primed State | 0.40 | 0.42 | HDAC1/NEAT1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-debate-20260406-062045-56983337 |
| h-b38d6762 | IRP2-Iron Axis Modulation to Reduce Ferroptotic Vulnerability | 0.40 | 0.48 | IRP2-Iron | proposed | 2026-04-25 | SDA-2026-04-17-gap-microglial-subtypes-pharmaco-202604170000 |
| h-9d07f0457a | IGFBPL1 Peptide Mimetics for Drug-Like BBB Permeability | 0.40 | 0.35 | IGFBPL1 | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062045-6addd0cf |
| h-a512eecb08 | CSF1R Inhibition Reversal Window Depends on Microglia Replacement Kinetics | 0.40 | 0.40 | CSF1R, nestin+ progenitor pool | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062045-7a6cf14e |
| h-b3ff662404 | USP13 Stabilization of PINK1/Parkin Mitophagy in Parkinson's Disease | 0.39 | 0.32 | USP13 | proposed | 2026-05-06 | SDA-2026-05-06-gap-test-20260425-224949 |
| h-var-ad33afddc6 | TBK1 Deficiency Disrupts Microglial Metabolic Reprogramming, Promoting Glycolyti | 0.39 | 0.34 | TBK1 → mTOR / ULK1 / AMPK / HIF-1α axis | proposed | 2026-04-26 | SDA-2026-04-26-gap-20260425215446 |
| h-ee19f160 | EZH2 Inhibitor Therapy to Restore Neuronal Identity Genes | 0.39 | 0.42 | EZH2 | proposed | 2026-04-25 | SDA-2026-04-16-gap-epigenetic-adpdals |
| h-da6c36b942 | Direct cystatin C inhibition of tau aggregation | 0.39 | 0.30 | CST3/MAPT interaction | proposed | 2026-04-25 | SDA-2026-04-26-gap-pubmed-20260410-150544-e3a2eab9-debate |
| h-3ccb92a780 | Exposure profile may matter more than nominal daily dose, but formulation optimi | 0.39 | 0.23 | EIF2AK3; EIF2S1 | proposed | 2026-04-25 | |
| h-351aa1a927 | Astrocyte-specific autophagy deficiency induces NADPH oxidase-mediated oxidative | 0.39 | 0.72 | ATG7 | proposed | 2026-04-27 | SDA-2026-04-08-gap-pubmed-20260406-062212-b66510d9 |
| h-aging-h2-synaptic- | Age-driven synaptic gene silencing precedes neuronal loss in vulnerable brain re | 0.39 | 0.75 | SYP | open | 2026-04-23 | aging-mouse-brain-2026-04-02 |
| h-5405873559 | BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic priming | 0.39 | 0.25 | ARNTL | proposed | 2026-04-21 | SDA-2026-04-07-gap-debate-20260406-062033-839c3e2a |
| h-var-b625142c91 | Dynamic Plasma Exosome-Derived Multi-Analyte Panel Combining YKL-40, sTREM2, and | 0.39 | 0.35 | CHI3L1/TREM2/NRGN | proposed | 2026-04-26 | SDA-2026-04-06-gap-debate-20260406-062039-3b945972 |
| h-var-4b83b3663c | Circulating hs-CRP as Disease-Modifying Target via Astrocytic Complement C3 Casc | 0.39 | 0.26 | CRP → C3 → C3aR/C5aR axis | proposed | 2026-04-26 | SDA-2026-04-16-frontier-immunomics-e6f97b29 |
| h-7ed5dae4 | TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signature Divergence" Dete | 0.39 | 0.17 | TDP, LATE, AD, RNA, SEA | active | 2026-04-25 | SDA-2026-04-25-gap-epi-clock-biomarker-20260425-222549 |
| h-e27562cbb4 | A-to-I RNA editing modulates the lncRNA-0021 binding site and tunes mmu-miR-6361 | 0.39 | 0.29 | ADAR1/ADAR2 | proposed | 2026-04-25 | SDA-2026-04-26-gap-pubmed-20260410-150509-76c40dac-debate |
| h-var-c995a1e28a | TREM2-Mediated Microglial Regulation of Oligodendrocyte Precursor Cell Maturatio | 0.38 | 0.34 | TREM2 | proposed | 2026-04-26 | SDA-2026-04-16-frontier-connectomics-84acb35a |
| h-24f6280d | Apolipoprotein E4-Mediated Metabolic Dysfunction Correction via Liver X Receptor | 0.38 | 0.50 | NR1H2 (LXRβ), APOE | proposed | 2026-04-25 | SDA-2026-04-16-frontier-metabolomics-f03b09d9 |
| h-7bb47d7a | Bacterial Enzyme-Mediated Dopamine Precursor Synthesis | 0.38 | 0.20 | TH, AADC | archived | 2026-04-02 | SDA-2026-04-01-gap-20260401-225155 |
| h-aging-h6-cars-risk | Composite Aging Risk Score (CARS) identifies hippocampus as the primary AD vulne | 0.38 | 0.76 | GFAP | proposed | 2026-04-27 | SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402 |
| h-var-e09a2c99ff | Astrocyte-Mediated Synaptic Tagging via CREB-S100B-RAGE Signaling | 0.38 | 0.26 | CREB1, S100B, AGER (RAGE) | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-var-6eb97ce157 | CREB-Mediated Differential CD55/CD46 Expression Creates Activity-Dependent Compl | 0.38 | 0.33 | CD55, CD46, CREB1 | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-var-838f64eb52 | Complement Regulator CD55/CD46 Expression Modulates Microglial Engulfment During | 0.38 | 0.33 | CD55 (DAF), CD46 (MCP) | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-var-abc42270c3 | Activity-Dependent Synaptic Tagging via CREB-IGF1-IGF1R Signaling | 0.38 | 0.26 | CREB1, IGF1, IGF1R | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-var-dbca541049 | CREB-Mediated Differential CD55/CD46 Expression Creates Activity-Dependent Compl | 0.38 | 0.33 | CREB1, CD55, CD46 | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-var-9d4a43c4ef | Astrocytic Complement Regulator Release Modulates Synaptic Vulnerability (CD55/C | 0.38 | 0.33 | CD55 (DAF), CD46 (MCP) | proposed | 2026-04-27 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |