Blocking early complement activation prevents microglia-mediated excessive synapse loss before and during amyloid deposition. C1q localized to synapses in early AD correlates with cognitive decline; C3 knockout or CR3 deficiency protects synapses in 5xFAD mice. Annexon's ANX005 anti-C1q antibody has human CNS target engagement experience from Huntington's disease trials.
No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for C1Q yet. Search RCSB →
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 C1Q.
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 patients with early-stage Alzheimer's disease (prodromal AD or MCI due to AD, confirmed by amyloid PET and CSF biomarkers) receive monthly intravenous ANX005 (anti-C1q) at 20 mg/kg for 12 months, T | CSF neurogranin concentration will be 30% lower in the treatment arm compared to placebo at month 18 | — no observation — | pending | 0.65 |
| IF 5xFAD mice receive intraperitoneal anti-C1q antibody (10 mg/kg, twice weekly) starting at 2 months of age and continuing for 6 months, THEN synaptic complement C3 deposition on hippocampal CA1 syna | Synaptic C3 fractional area on hippocampal CA1 neurons will be reduced by ≥50% in anti-C1q treated mice vs. control | — no observation — | pending | 0.78 |