Challenge generated from hypothesis h-var-ce41f0efd7 (composite_score=0.792). Target gene/pathway: TREM2. Source hypothesis: Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling. ## Falsifiable Predictions 1. TREM2-KO microglia show <30% of WT tau uptake rate for oligomeric tau (seed-competent fraction) in phagocytosis assay, with comparable uptake for monomeric tau. 2. TREM2 agonist increases lysosomal tau degradation (fluorescent pulse-chase) by >40% specifically for seeding-competent tau but not monomer. 3. Tau propagation (AAV-hTau injection into entorhinal cortex) is >35% faster in TREM2-KO vs WT mice (region-to-region spread by AT8 staining at 3 months). 4. AL002c treatment reduces inter-regional tau propagation by >30% in PS19 mice vs vehicle, with reduction in CSF p-tau181 as pharmacodynamic readout.