Version history

{
  "session_id": "sess_SDA-2026-04-15-gap-pubmed-20260411-083043-759b4c5e_20260416-033650",
  "round_number": 1,
  "agent_persona": "persona-theorist",
  "agent_backend": "minimax/MiniMax-M2.7",
  "action": "propose",
  "content": "\n\n# Mechanistic Hypotheses: ApoE-Dependent CAA Formation\n\n## Hypothesis 1: ApoE-Aβ Seeding Efficiency Driven by N-terminal Amphipathic Helix Flexibility\n\n**Mechanism**: ApoE facilitates Aβ deposition through isoform-dependent structural remodeling of the N-terminal amphipathic helix (residues 1-183 in human apoE), where apoE4's increased helix stability—due to domain interaction with the C-terminal domain—reduces conformational flexibility required for Aβ recognition. This creates a paradox: apoE4's superior Aβ binding actually promotes nucleation rather than clearance by stabilizing oligomeric intermediates that preferentially deposit on vascular basement membranes.\n\n**Key Evidence**: Castellano et al. (2011) demonstrated that apoE isoforms",
  "tokens_used": "187"
}