Challenge generated from hypothesis SDA-2026-04-02-gap-tau-prop-20260402003221-H002 (composite_score=0.780). Target gene/pathway: TREM2. Source hypothesis: TREM2-mediated microglial tau clearance enhancement. ## Falsifiable Predictions 1. TREM2 agonist increases uptake of fibrillar tau seeds (pre-formed fibrils, PFF) by >50% in primary microglia vs vehicle (flow cytometry bead assay). 2. Microglial tau phagocytosis is TREM2-dependent (TREM2-KO shows <20% of WT uptake); specificity confirmed by TREM2-KO rescue with TREM2 re-expression. 3. In PS19 tauopathy mice (amyloid-free model), AL002c or equivalent TREM2 agonist reduces tau spread from EC to hippocampus by >30% vs vehicle (AT8 staining at 6 months). 4. CSF sTREM2 levels increase >1.5-fold after TREM2 agonist treatment in PS19 mice, providing a pharmacodynamic biomarker of target engagement.