This challenge targets the hypothesis: **C1QA/C1QB Subunit-Specific Inhibition to Block Aberrant PV Interneuron Input Elimination in Alzheimer's Disease** **Hypothesis Summary:** **Molecular Mechanism and Rationale** The complement system's classical pathway, initiated by C1q complex formation, represents a critical convergence point between innate immunity and synaptic plasticity in the central nervous system. The C1q complex consists of three distinct subunits—C1QA, C1QB, and C1QC—that form a hexameric structure (A₂B₂C₂) essential for complement activation. In Alzheimer's disease pathophysiology, aberrant complement activation drives circuit-specific synaptic eliminat **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:** $124,700 USD (composite score 0.747) **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.