Enhancing TREM2 signaling shifts microglia toward a neuroprotective state with improved lipid metabolism, enhanced phagocytosis of amyloid plaques, and reduced neurotoxicity. TREM2 R47H variants confer ~3-fold AD risk. Agonistic antibodies developed by Alector/AbbVie showed target engagement but AL002 Phase 2 failed to meet primary clinical endpoints.
No linked papers recorded for this hypothesis yet.
No clinical trials data linked to this hypothesis yet.
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 TREM2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No resource usage or linked notebooks recorded for this hypothesis yet.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF AD patients (n≥120, aged 55-85, amyloid-positive by PET, including ≥40 with TREM2 R47H/R47H or R47H/wt genotype) receive a TREM2 agonistic antibody (AL002 or bioequivalent) at 10mg/kg IV every 4 we | ≥50% increase in CSF sTREM2; ≥15% decrease in plasma NfL in TREM2 R47H carriers | — no observation — | pending | 0.45 |
| IF a selective TREM2 agonist (e.g., AL002 or a surrogate compound) is administered to 5xFAD mice (n≥15/group) for 12 weeks starting at 4 months of age, THEN hippocampal amyloid plaque burden will decr | ≥30% reduction in amyloid plaque density in hippocampus; ≥2-fold increase in microglial TREM2 pathway activation markers | — no observation — | pending | 0.55 |