This challenge targets the hypothesis: **CX3CR1-TREM2 Integration for Synapse Pruning Normalization** **Hypothesis Summary:** ## Mechanistic Overview CX3CR1-TREM2 Integration for Synapse Pruning Normalization starts from the claim that modulating CX3CR1-TREM2 within the disease context of neurodegeneration can redirect a disease-relevant process. The original description reads: "**Molecular Mechanism and Rationale** The CX3CR1-TREM2 integration hypothesis centers on the sophisticated crosstalk between two critical microglial receptors that collectively establish a molecular rheostat governing synapse pruning in the cen **Falsifiable Predictions:** 1. Pharmacological modulation of CX3CR1-TREM2 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:** $127,600 USD (composite score 0.776) **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.