Resolve: Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes

Falsifiable prediction from high-scoring hypothesis (score=0.728, gene=NR1H2 (LXRβ), ABCA1, ABCG1). Hypothesis: Can selective LXRβ agonism restore cholesterol efflux in APOE4 astrocytes by upregulating ABCA1/ABCG1, normalizing APOE lipidation, and reducing amyloid-driven neurotoxicity? Success criteria: 1. LXRβ-selective agonist (e.g., BMS-986192) increases ABCA1/ABCG1 mRNA >2-fold in APOE4 iPSC-astrocytes vs vehicle. 2. APOE4 lipidation state (HDL-sized particles) improves by >35% after 48h LXRβ agonist treatment. 3. Conditioned media from LXRβ-treated APOE4 astrocytes reduces amyloid-beta toxicity in neuronal co-culture by >30% vs untreated. 4. In vivo: 5xFAD/APOE4 KI mice show >25% reduction in cortical plaque load after 12-week LXRβ agonist treatment.