This challenge targets the hypothesis: **Selective blockade of classical-pathway activation downstream of C1q will reduce synaptotoxic complement amplification while preserving beneficial C1q recognition functions** **Hypothesis Summary:** The most actionable synthesis is that pathogenicity may depend more on conversion of C1q binding into classical-pathway protease activity than on C1q recognition alone. In this model, inhibiting C1r/C1s should attenuate C4/C3-mediated synapse loss and neuroinflammation while preserving some homeostatic debris sensing and cargo recognition by C1q. **Falsifiable Predictions:** 1. Pharmacological modulation of C1QA will alter neurodegeneration markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $125,000 USD (composite score 0.750) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.