Curated pathway from expert analysis
flowchart TD
A["APOE e4 Isoform<br/>Reduced TREM2 Binding Affinity"]
B["TREM2 Lipid Sensing Impaired<br/>Microglial Lipid Metabolism Deficit"]
C["APOE Mimetic Peptide<br/>Restores APOE-TREM2 Interaction"]
D["TREM2 Co-Activator Compound<br/>Receptor Stabilization and Signaling"]
E["Dual Therapy Synergy<br/>APOE Mimetic plus TREM2 Co-Activator"]
F["Microglial Cholesterol Efflux Restored<br/>Lipid Droplet Burden Reduced"]
G["Amyloid-Beta Phagocytosis Enhanced<br/>Plaque Clearance Improved"]
H["Neuroinflammation Resolved<br/>AD Neuroprotection"]
A --> B
C --> E
D --> E
E --> F
E --> G
F --> H
G --> H
style E fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ['APOE' yet. Search RCSB →
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ['APOE', 'TREM2'].
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF iPSC-derived microglia from APOE4/4 carriers are treated with combined APOE mimetic (1 μM COG1410) and TREM2 agonistic antibody (10 μg/mL) for 72 hours during exposure to fluorescently-labeled Aβ42 | ≥40% reduction in internalized Aβ42 fluorescence and ≥50% increase in lipid droplet area per microglia cell | — no observation — | pending | 0.00 |
| IF aged 5xFAD mice (8 months) receive combined intraperitoneal APOE mimetic peptide (COG1410, 2 mg/kg) and TREM2-activating antibody (2 mg/kg, biweekly) for 12 weeks, THEN amyloid plaque coverage in c | ≥30% reduction in amyloid plaque area fraction in cortical and hippocampal regions after 12-week combination treatment | — no observation — | pending | 0.00 |