This challenge targets the hypothesis: **sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy** **Hypothesis Summary:** ## Mechanistic Overview sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy starts from the claim that modulating not yet specified within the disease context of neurodegeneration can redirect a disease-relevant process. The original description reads: "sTREM2 as Biomarker of Cystatin-C Therapeutic Efficacy Mechanism of Action The intersection between cystatin-C and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) represents a compelling mechanistic node at the nexus of micro **Falsifiable Predictions:** 1. Pharmacological modulation of 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:** $125,663 USD (composite score 0.757) **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.