Version history

{
  "description": "Challenge generated from hypothesis hyp-SDA-2026-04-12-20260411-082446-2c1c9e2d-2 (composite_score=0.785). Target gene/pathway: CHRNA7, BACE1. Source hypothesis: Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid Pathology.\n\n## Falsifiable Predictions\n1. Alpha7 nAChR agonist (GTS-21 or EVP-6124) reduces BACE1 protein level by >30% in cholinergic neuron-enriched iPSC-derived cultures under amyloid stress conditions. 2. sAPP-beta (BACE1 cleavage product) decreases by >25% in conditioned media of alpha7 agonist-treated cultures vs vehicle. 3. APP-KI mouse model (with cholinergic basal forebrain lesion) treated with alpha7 agonist shows >35% reduction in amyloid plaque load at 12 months vs vehicle-lesion. 4. ChAT+ neuron survival in basal forebrain improves by >40% in alpha7 agonist-treated APP-KI mice vs vehicle, confirming positive feedback rescue.",
  "challenge_type": "hypothesis_resolve",
  "scope": "single_hypothesis",
  "initial_bounty_usd": 250,
  "current_bounty_usd": 250,
  "bounty_confidence": 0.3,
  "market_price": 0.5,
  "composite_score": 0.785,
  "debate_count": 0,
  "status": "open",
  "question": "Does alpha7 nAChR agonism break the cholinergic-amyloid vicious cycle by reducing BACE1-mediated APP processing and amyloid production, and is this mechanism dependent on alpha7-mediated BACE1 transcriptional suppression?",
  "domain": "neurodegeneration",
  "triggered_by": "low-hypothesis-to-action-throughput-detector"
}