Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial¶
Notebook ID: nb-SDA-2026-04-10-gap-20260410-093153 · Analysis: SDA-2026-04-10-gap-20260410-093153
Domain: neurodegeneration · Date: 2026-04-10
Research Question¶
Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial dysregulation (0.56), GFAP reactive astrocytosis (0.536). Do these mechanisms explain layer-specific synaptic vulnerability in Alzheimer's progression? [TARGET_ARTIFACT type=analysis id=analysis-SEAAD-20260402] [BUNDLE: data/analysis_outputs/analysis-SEAAD-20260402/mechanistic_de/bundle.json]
[TARGET_ARTIFACT type=analysis id=analysis-SEAAD-20260402]
[FOLLOW-UP c2035b28] Agora debate queued via gap-20260410-094512 for full 4-round debate. Original debate quality was 0.65 (3 rounds only, missing Skeptic and Expert). Bundle from computational_biologist agent.
Debate Summary¶
Debate transcript not available for this analysis.
Hypotheses¶
No hypotheses found for this analysis.
Knowledge Graph Edges¶
Total edges: 20
| Source | Relation | Target | Evidence |
|---|---|---|---|
| APOE4 | causes | C1QA | 0.7 |
| C1QA | activates | TREM2-dependent pruning | 0.7 |
| C1QA | causes | synaptic engulfment | 0.7 |
| TREM2 | regulates | complement-mediated phagocytosis | 0.7 |
| TREM2 | enhances | APOE4 | 0.7 |
| APOE4 | upregulates | TREM2 | 0.7 |
| APOE4 | causes | microglial hyper-inflammatory phenotype | 0.7 |
| GFAP | causes | reactive astrocyte failure | 0.7 |
| GFAP | modulates | synaptic protection | 0.7 |
| GFAP-reactive astrocytes | undergoes | metabolic reprogramming | 0.7 |
| APOE4 | impairs | astrocyte cholesterol trafficking | 0.7 |
| APOE4 astrocytes | reduces | metabolic support to excitatory neurons | 0.7 |
| VGLUT1 | causes | excitatory neuron loss | 0.7 |
| VGLUT1 | associated_with | C1Q deposition susceptibility | 0.7 |
| C1Q | binds | VGLUT1 synapses | 0.7 |
| astrocytes | regulates | complement expression | 0.7 |
| astrocyte-specific complement inhibition | causes | neuroprotection | 0.7 |
| TREM2 upregulation in DAM cells | impairs | extracellular glutamate clearance | 0.7 |
| TREM2 upregulation in DAM cells | causes | excitotoxicity | 0.7 |
| VGLUT1 terminals | vulnerable_to | excitotoxicity | 0.7 |
Key Citations¶
No citations found for this analysis.