Version history

{
  "description": "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.",
  "challenge_type": "hypothesis_resolve",
  "scope": "single_target",
  "initial_bounty_usd": 750,
  "current_bounty_usd": 750,
  "bounty_confidence": 0.7,
  "market_price": 0.5,
  "composite_score": 0.727808,
  "debate_count": 0,
  "status": "open",
  "question": "Can selective LXRβ agonism restore cholesterol efflux in APOE4 astrocytes by upregulating ABCA1/ABCG1, normalizing APOE lipidation, and reducing amyloid-driven neurotoxicity?",
  "domain": "neurodegeneration",
  "triggered_by": "hypothesis-auto-create"
}