| h-e165e0e6 | PGC1α Activation in PV+ Interneurons Bypasses Mitophagy Deficit to Restore Gamma | 0.46 | 0.50 | PPARGC1A | proposed | 2026-04-15 | SDA-2026-04-15-gap-pubmed-20260411-082509-118fcb37 |
| h-f78067ba | GM1 Ganglioside Reduction via ST3GAL5 Activation to Block Aβ Oligomerization See | 0.45 | 0.50 | ST3GAL5 | proposed | 2026-04-26 | SDA-2026-04-16-frontier-lipidomics-dcdbc360 |
| h-69acbe8b | P2X7 Receptor Antagonism to Block ATP-Induced Microglial Pyroptosis | 0.45 | 0.45 | P2RX7 (P2X7 receptor) → PANX1 → NLRP3 → Caspase-1/Gasdermin | proposed | 2026-04-26 | SDA-2026-04-16-frontier-immunomics-e6f97b29 |
| h-var-7b37ca6d98 | SREBP-2 Upstream Modulation for APOE4 Lipidation Enhancement | 0.45 | 0.38 | SREBP-2/SCAP | promoted | 2026-04-21 | SDA-2026-04-16-gap-debate-20260410-113104-a13caf2e |
| h-var-6856106f48 | Mitochondrial Damage-Triggered SPP1 Inflammasome Coupling | 0.45 | 0.39 | SPP1 | promoted | 2026-04-21 | SDA-2026-04-15-gap-pubmed-20260406-062118-e3613755 |
| h-645cc2de | TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic Clearance | 0.45 | 0.65 | TREM2 (Triggering receptor expressed on myeloid cells 2) + S | proposed | 2026-04-14 | SDA-2026-04-13-gap-pubmed-20260410-165345-41805e1b |
| h-3ae038e731 | Age-dependent downregulation of KPNA2 creates limbic neuron-specific nuclear imp | 0.45 | 0.45 | KPNA2 (karyopherin α2) | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062202-094b44bf |
| h-404bab00 | Age-Stratified Ketone Dosing Matrix | 0.45 | 0.20 | OXCT1 | proposed | 2026-04-17 | SDA-2026-04-03-gap-debate-20260403-222618-2709aad9 |
| h-0c68c97b58 | Astrocyte Heterogeneity and Synapse-Specific Eat-Me Signal Expression | 0.45 | 0.40 | MFGE8, NPTX2 (Neuronal Pentraxin 1) | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9 |
| h-00d4ef329d | SST-Microglial CRHR1-SSTR2 Neuroimmune Cross-Talk (Secondary Hypothesis) | 0.45 | 0.45 | CRHR1, SST, SSTR2; NF-κB, TNF-α | proposed | 2026-04-28 | SRB-2026-04-28-h-var-b7e4505525 |
| h-255db681 | HDAC6 Inhibitor Therapy for Pan-Neurodegenerative Protein Homeostasis | 0.45 | 0.48 | HDAC6 | proposed | 2026-04-26 | SDA-2026-04-16-gap-epigenetic-adpdals |
| h-85753bf7db | HBOT at 2.0 ATA for 60 min, 5x/week for 6 weeks enhances hippocampal neurogenesi | 0.45 | 0.42 | BDNF | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260410-181340-8acb24dc-debate |
| h-63ef3ee258 | Amyloid first impairs cholinergic terminals through alpha7 nicotinic receptor-de | 0.45 | 0.46 | APP, CHRNA7 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-e849205bca |
| h-8b269886b2 | α4β1 Integrin (VLA-4) and JAK/STAT Pathway | 0.45 | 0.50 | ITGA4, ITGB1 (α4β1 heterodimer), JAK1/JAK2, STAT3 | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-062118-e3613755 |
| h-945bac1144 | Metabolic Reprogramming Toward GAPDH Inhibition | 0.45 | 0.35 | GAPDH, HK2 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062150-a6cc7467 |
| h-ee8027e768 | Astrocytic APOE4 Disruption of GABAergic Support Increasing Neuronal Vulnerabili | 0.45 | 0.35 | SLC1A2 (GLT-1), GABRA1, GABRB3, GAD1 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062202-c8c5a9a1 |
| h-71d9c1103e | Parallel Multi-Pathway Convergence on TFEB Activation | 0.45 | 0.40 | Multiple convergence points; TFEB as master regulator | proposed | 2026-04-21 | SDA-2026-04-08-gap-pubmed-20260406-062150-5b7d1556 |
| h-32a6b226a4 | Paraneoplastic myelopathies involve CD8+ T cell recognition of viral/cancer anti | 0.45 | 0.38 | HLA-A, HLA-B, CD8A, CD8B, PRF1, GZMB, RIPK3, MLKL | proposed | 2026-04-21 | SDA-2026-04-08-gap-pubmed-20260406-062111-e3e328bf |
| h-var-ac595654ef | CSF Neurofilament Light-Triggered Astrocyte-Derived Exosome Dosing Maximizes lnc | 0.45 | 0.36 | CSF neurofilament light (biomarker), lncRNA-0021, astrocyte- | promoted | 2026-04-21 | SDA-2026-04-16-gap-pubmed-20260410-150509-76c40dac |
| h-fef1b822 | Hsp70 cochaperone BAG3-mediated Autophagy Activation for Synaptic Protein Qualit | 0.45 | 0.47 | BAG3 (Bcl-2-associated athanogene 3) | proposed | 2026-04-26 | SDA-2026-04-16-frontier-proteomics-1c3dba72 |
| h-var-787004e57a | Astrocytic SPP1 Modulation for Neuroinflammatory Resolution | 0.45 | 0.56 | SPP1 | promoted | 2026-04-21 | SDA-2026-04-15-gap-pubmed-20260406-062118-e3613755 |
| h-SDA-2026-04-26-gap | eIF2alpha Dephosphorylation Threshold Prevents Pro-Apoptotic ATF4/CHOP Activatio | 0.45 | 0.38 | p-eIF2alpha (Ser51), ATF4, CHOP (DDIT3) | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260411-081101-dfe3eacb |
| h-SDA-2026-04-26-gap | Time-Restricted High-Dose Melatonin for Acute Neuroprotection | 0.45 | 0.38 | MT1 receptor; CHOP (DDIT3); caspase-12; Bcl-2/Bax | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260411-090734-1be1b913 |
| h-var-ad7d733b0d | C1q-Alectinib Complexation Disrupts Tight Junction Integrity to Enable Paracellu | 0.44 | 0.33 | CLDN5, OCLN | proposed | 2026-04-20 | SDA-2026-04-17-gap-debate-20260417-033037-c43d12c2 |
| h-440f8a5f | MITF Acts as the Primary Transcriptional Effector Downstream of HDAC1/2 Deletion | 0.44 | 0.35 | MITF | proposed | 2026-04-13 | SDA-2026-04-13-gap-pubmed-20260410-110327-26e1d6c7 |
| h-f5518156 | Microglial Membrane Camouflage Exploits CD47-SIRPα Checkpoint Disinhibition | 0.44 | 0.40 | CD47, SIRPA, PTPN6, PTPN11 | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-095709-4e97c09e |
| h-b4bec30ca0 | α-Ketoglutarate/2-HG Metabolic-Epigenetic Window in Neurons | 0.44 | 0.45 | 2-HG/KDM4B | proposed | 2026-04-21 | SDA-2026-04-07-gap-debate-20260406-062039-7ef9980b |
| h-df966dc049 | RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivasc | 0.44 | 0.40 | SPP1 | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-062118-5e49e14f |
| h-803b338102 | Monocyte Trojan Horse Cell Therapy | 0.44 | 0.45 | IGFBPL1 | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062045-6addd0cf |
| h-3c562f5aff | Reactive astrocytes and cholinesterase-rich low-acetylcholine niches amplify tau | 0.44 | 0.34 | BCHE, ACHE, GSK3B, CDK5 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-e849205bca |
| h-5d374a18a2 | Propionate may outperform acetate or butyrate at physiological exposure, but mai | 0.44 | 0.32 | FFAR3/STAT3 | proposed | 2026-04-25 | SDA-2026-04-25-gapdebate-18cce7b525 |
| h-b5bb5945ca | Casein Kinase 2 (CK2)-Mediated Hyperphosphorylation of G3BP1 Blocks TRIM21 Acces | 0.44 | 0.45 | G3BP1, CSNK2A1 (CK2) | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-041423-3a6aa4ab |
| h-bc1a278bd9 | DNA Hypomethylation at P2RY12 Promoter Correlates with Disease Progression | 0.44 | 0.38 | DNMT1, TET2 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041434-a4d6154a |
| h-7d9d862d6d | KLF4-Mediated Transcriptional Repression of P2RY12 | 0.44 | 0.38 | KLF4 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-041434-a4d6154a |
| h-495e04396a | Vagus Nerve as Anatomical Highway for Prion-Like α-Syn Propagation | 0.44 | 0.45 | SNCA/p-SNCA (Ser129)/GBA/LRRK2 | proposed | 2026-04-26 | SDA-2026-04-26-gut-brain-pd-ffdff6f4 |
| h-var-7153fe21b9 | Epigenetic Silencing of Tumor Suppressor Genes in Cancer Progression | 0.44 | 0.30 | TP53 | archived | 2026-04-21 | |
| hyp_test_2750d4e9 | Test: TREM2 enhances amyloid clearance | 0.44 | 0.30 | TREM2 | proposed | 2026-04-17 | test-hypothesis-fixtures-v1 |
| h-6fa7dbdb88 | Seed Conformational Heterogeneity Explains Variable Chaperone Susceptibility—Str | 0.44 | 0.50 | DNAJC7, PTGDS, tau conformers | proposed | 2026-04-22 | SDA-2026-04-06-gap-debate-20260406-062052-28cbc764 |
| h-4682ee7fdf | Parthenolide changes ADORA2A coupling efficiency through membrane microdomain re | 0.44 | 0.38 | ADORA2A | proposed | 2026-04-26 | SDA-2026-04-26-gap-pubmed-20260410-193037-1dc5e03a-debate |
| h-c27bd44a | Cathepsin D Replacement to Overcome Lysosomal Protease Deficiency | 0.43 | 0.48 | CTSD (cathepsin D) | proposed | 2026-04-26 | SDA-2026-04-16-frontier-proteomics-1c3dba72 |
| h-var-981a915d51 | Alpha-Beta Oscillation Entrainment Enhances lncRNA-9969-Mediated Mitochondrial B | 0.43 | 0.33 | SST, CREB1, lncRNA-9969, PGC1α, TFAM, NRF1 | proposed | 2026-04-17 | SDA-2026-04-16-gap-pubmed-20260410-150509-76c40dac |
| h-b8cedff2 | Fecal Microbiota Transplantation to Reset Microglial Priming States | 0.43 | 0.35 | Gut microbiome → LPS/TMAO → HDAC6 → Microglial NF-κB | proposed | 2026-04-26 | SDA-2026-04-16-frontier-immunomics-e6f97b29 |
| h-var-38b7c84a38 | Gamma-Entrained P-tau217 Biomarker Cascades Optimize lncRNA-9969 Exosome Therapy | 0.43 | 0.50 | lncRNA-9969 | promoted | 2026-04-21 | SDA-2026-04-16-gap-pubmed-20260410-150509-76c40dac |
| h-4c4bf4a28f | FUS Mutations Impede G3BP1's Chaperone Function, Exposing Neurotoxic Stress Gran | 0.43 | 0.45 | FUS | proposed | 2026-04-22 | SDA-2026-04-06-gap-pubmed-20260406-041428-e14e6524 |
| h-0e1b168576 | Blood-Brain Barrier Disruption Enabling Peripheral Inflammatory Insult | 0.43 | 0.38 | PDGFRB, CLDN5, OCLN, FGB | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062202-c8c5a9a1 |
| h-a3a9b0941b | DNA Damage Repair Dysfunction Creating TDP-43 Pathology Feed-Forward Loop | 0.43 | 0.32 | PARP1, ATM, XRCC1, LIG3 | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062202-c8c5a9a1 |
| h-58626a052a | Calcineurin-FUNDC1 Axis as a Master Switch for Mitophagy vs. Apoptotic Cell Deat | 0.43 | 0.38 | PPP3CA (Calcineurin A) | proposed | 2026-04-21 | SDA-2026-04-08-gap-pubmed-20260406-062132-5d93ddb2 |
| h-ae112108 | GABAergic Hub Stabilization Through α5-Subunit Inverse Agonists | 0.43 | 0.45 | GABAergic Hub Stabilization | proposed | 2026-04-26 | SDA-2026-04-16-frontier-connectomics-84acb35a |
| h-96f0af34 | GSK3β Inhibition to Prevent α-Synuclein Phosphorylation and Aggregation | 0.43 | 0.35 | | proposed | 2026-04-18 | SDA-2026-04-17-gap-pubmed-20260410-145520-5692b02e |
| h-2aa8f74e75 | Source-Specific SPP1 Inhibition: Perivascular Cell Targeting | 0.43 | 0.42 | SPP1 (perivascular) | proposed | 2026-04-21 | SDA-2026-04-07-gap-pubmed-20260406-062118-2cdbb0dd |