| h-cross-synth-tdp43- | TDP-43 RNA-proteostasis failure across ALS, FTD, and AD/LATE | 0.83 | 0.86 | TARDBP | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-var-ce41f0efd7 | Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling | 0.83 | 0.75 | TREM2 | promoted | 2026-04-07 | SDA-2026-04-03-26abc5e5f9f2 |
| h-var-9e8fc8fd3d | Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla | 0.83 | 0.45 | PVALB | promoted | 2026-04-16 | SDA-2026-04-03-26abc5e5f9f2 |
| h-var-d33964b962 | Real-time gamma-guided transcranial focused ultrasound targeting EC-II SST inter | 0.83 | 0.45 | SST | proposed | 2026-04-07 | SDA-2026-04-03-26abc5e5f9f2 |
| h-var-a0933e666d | Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuro | 0.82 | 0.76 | AIM2, CASP1, IL1B, PYCARD, TARDBP | proposed | 2026-04-05 | SDA-2026-04-01-gap-20260401-225149 |
| h-22d2cfcd | SIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via | 0.82 | 0.50 | SIRT1 and PGC1alpha (PPARGC1A) axis | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef |
| h-alsmnd-e448328ae29 | GLE1-Mediated mRNA Export Defect Creates Translation-Competent mRNA Starvation i | 0.82 | 0.75 | GLE1,DBP10,EXPORTIN-1,XPO1,mRNA export machinery,NPC | open | 2026-04-28 | |
| h-var-adfecef68a | Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates | 0.82 | 0.78 | NLRP3, CASP1, IL1B, PYCARD | proposed | 2026-04-05 | SDA-2026-04-01-gap-20260401-225149 |
| h-856feb98 | Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation | 0.82 | 0.78 | BDNF | promoted | 2026-04-02 | SDA-2026-04-03-26abc5e5f9f2 |
| h-ff0d545d | HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase | 0.82 | 0.68 | HSPB1 | promoted | 2026-04-13 | SDA-2026-04-12-gap-debate-20260410-113051-5dce7651 |
| h-b007ca967f | Autophagy-Lysosomal Pathway Dysfunction as a Unifying Proteostasis Failure | 0.82 | 0.78 | TFEB, GBA1, VPS35, TMEM175 | proposed | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-cross-synth-snca-s | SNCA conformer propagation across PD, DLB, and MSA | 0.82 | 0.84 | SNCA | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-cross-synth-c9orf7 | C9ORF72 autophagy-lysosome collapse across ALS and FTD | 0.82 | 0.83 | C9ORF72 | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| SDA-2026-04-02-gap-t | Extracellular Vesicle Biogenesis Modulation | 0.81 | 0.57 | CHMP4B | proposed | 2026-04-17 | SDA-2026-04-04-gap-tau-prop-20260402003221 |
| h-cross-synth-mapt-t | MAPT tau seeding and release across AD, FTD, and PD-spectrum disease | 0.81 | 0.82 | MAPT | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-5d100034 | SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent N | 0.81 | 0.47 | SLC7A11 (system Xc-) and GPX4 | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef |
| h-0bcda2e0 | CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerabilit | 0.81 | 0.78 | APOE, CLU | promoted | 2026-04-16 | SDA-2026-04-15-gap-debate-20260410-112607-0a3749ea |
| h-var-14d7585dd1 | Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and bl | 0.81 | 0.82 | PVALB | promoted | 2026-04-05 | SDA-2026-04-03-26abc5e5f9f2 |
| h-alsmnd-54f981ca6a2 | TIA1 Low-Complexity Domain Oxidation Drives Aberrant Stress Granule Assembly and | 0.81 | 0.75 | TIA1,TDP-43,TARDBP,G3BP1,MAPK1,Oxidative stress response | open | 2026-04-28 | |
| SDA-2026-04-02-gap-t | LRP1-Dependent Tau Uptake Disruption | 0.81 | 0.72 | LRP1 | promoted | 2026-04-17 | SDA-2026-04-04-gap-tau-prop-20260402003221 |
| h-0cbe9bac | CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion | 0.81 | 0.52 | CSF1R-TREM2 | proposed | 2026-04-17 | SDA-2026-04-01-gap-001 |
| h-9268cd08d2 | Thalamocortical Feedforward Inhibition Imposes Rhythm on Glymphatic Waste Cleara | 0.81 | 0.85 | GRIN2B (VB thalamocortical relay neurons); circuit-level tar | proposed | 2026-04-28 | SRB-2026-04-28-h-var-e2b5a7e7db |
| h-5b35f7a5 | Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to Neuro | 0.81 | 0.62 | HCAR2 | promoted | 2026-04-16 | SDA-2026-04-15-gap-debate-20260410-112330-9abf86eb |
| h-3b539acf | Neutrophil Extracellular Trap (NET) Inhibition | 0.81 | 0.86 | PADI4 | proposed | 2026-04-16 | SDA-2026-04-16-gap-bbb-tjp-20260416041707 |
| h-var-6957745fea | Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration | 0.81 | 0.75 | AIM2, CASP1, IL1B, PYCARD | proposed | 2026-04-05 | SDA-2026-04-01-gap-20260401-225149 |
| h-cross-synth-trem2- | TREM2-APOE microglial state switching across AD, ALS, and PD | 0.80 | 0.80 | TREM2 | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-var-af9eb8e59b | Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for | 0.80 | 0.75 | AIM2, CASP1, IL1B, PYCARD, PPIF | proposed | 2026-04-05 | SDA-2026-04-01-gap-20260401-225149 |
| h-2e03f316 | TREM2-mTOR Co-Agonism for Metabolic Reprogramming | 0.80 | 0.60 | TREM2-mTOR pathway | proposed | 2026-04-17 | SDA-2026-04-01-gap-001 |
| h-48d1115a | Dual-Receptor Antibody Shuttling | 0.80 | 0.45 | | proposed | 2026-04-13 | |
| h-d47c2efa | Targeting the Mechanistic Link Between AQP4 Dysfunction and Ferroptosis Prevents | 0.80 | 0.52 | AQP4 and ACSL4 (key ferroptosis regulator) | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef |
| h-var-d04a952932 | Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neurodegeneration | 0.80 | 0.74 | AIM2, CASP1, IL1B, PYCARD | superseded | 2026-04-05 | SDA-2026-04-01-gap-20260401-225149 |
| h-alsmnd-01446b71d93 | MATR3 Nuclear Body Disruption Impairs RNA Processing Hubs and Triggers Splicing | 0.80 | 0.75 | MATR3,U1 snRNP,SNRPB,SNRNP70, splicing machinery,spliceosome | open | 2026-04-28 | |
| h-620a7b5b79 | Gamma entrainment repairs cross-regional phase-amplitude coupling via CA1 Schaff | 0.80 | 0.82 | GRIN2A/GRIN2B (NR2A/NR2B NMDA receptors), CAMK2A | proposed | 2026-04-28 | SRB-2026-04-28-h-bdbd2120 |
| h-7d24e096 | CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification | 0.80 | 0.80 | sTREM2/membrane-TREM2/ADAM10 | promoted | 2026-04-16 | SDA-2026-04-26-trem2-showcase |
| h-var-22c38d11cd | ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen | 0.80 | 0.87 | ACSL4 | debated | 2026-04-05 | SDA-2026-04-03-gap-seaad-v4-20260402065846 |
| h-var-261452bfb4 | 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively | 0.80 | 0.87 | ACSL4 | debated | 2026-04-05 | SDA-2026-04-03-gap-seaad-v4-20260402065846 |
| h-cross-synth-nlrp3- | NLRP3 inflammasome amplification across AD and PD proteinopathy | 0.80 | 0.79 | NLRP3 | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-7e9718dbda | pH-Sensitive Bispecific Antibody Targeting Transferrin Receptor for CNS Delivery | 0.80 | 0.33 | TFRC (TfR1); endosomal acidification pathway | proposed | 2026-04-22 | SDA-2026-04-02-gap-bbb-antibody-transport |
| h-f32ba823 | Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective Effector | 0.80 | 0.52 | MANF, CDNF | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-170057-a2f72fd8 |
| h-48858e2a | Microglial TREM2-SYK Pathway Enhancement | 0.80 | 0.70 | TREM2 | promoted | 2026-04-14 | SDA-2026-04-03-gap-seaad-v4-20260402065846 |
| h-var-ee70969116 | Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with r | 0.80 | 0.45 | PVALB | proposed | 2026-04-07 | SDA-2026-04-03-26abc5e5f9f2 |
| h-cross-synth-pink1- | PINK1/Parkin mitophagy failure across PD, AD, and ALS | 0.80 | 0.78 | PINK1;PARK2 | active | 2026-04-28 | SDA-2026-04-28-cross-disease-synthesis |
| h-11795af0 | Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs) | 0.79 | 0.30 | APOE | promoted | 2026-04-02 | sda-2026-04-01-gap-010 |
| h-a9f2570b | Targeting SASP-Complement Amplification Through HIF-1α Downstream Effectors | 0.79 | 0.68 | C1QA, C1QB, C3, IL1B | promoted | 2026-04-14 | SDA-2026-04-13-gap-pubmed-20260410-170057-1bea7d88 |
| h-3f02f222 | Senescent Microglia Resolution via Maresins-Senolytics Combination | 0.79 | 0.60 | BCL2L1 | debated | 2026-04-02 | sda-2026-04-01-gap-014 |
| h-ac41e5c23d | Exposed amyloidogenic segments (β-sheet propensity residues) serve as HSP70 reco | 0.79 | 0.72 | HSPA8, HSPA1A, DNAJB6, DNAJB2 | proposed | 2026-04-21 | SDA-2026-04-10-gap-debate-20260410-075012-32bac138 |
| h-d4ac0303f6 | G2019S primarily raises baseline LRRK2 kinase activity rather than amplifying ly | 0.79 | 0.32 | LRRK2 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-9180363b7c |
| h-da9af6a77a | NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic Axis and Dopaminergic | 0.79 | 0.73 | SIRT1/NAD+ axis | proposed | 2026-04-22 | SDA-2026-04-04-gap-20260404-060512 |
| h-f3fb3b91 | Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory Priming | 0.79 | 0.60 | TLR4 | proposed | 2026-04-03 | SDA-2026-04-01-gap-20260401-225149 |
| SDA-2026-04-02-gap-t | VCP-Mediated Autophagy Enhancement | 0.79 | 0.53 | VCP | proposed | 2026-04-17 | SDA-2026-04-04-gap-tau-prop-20260402003221 |