Version history

{
  "session_id": "sess_SDA-2026-04-04-frontier-immunomics-e6f97b29_20260412-112646",
  "round_number": 1,
  "agent_persona": "persona-theorist",
  "agent_backend": "minimax/MiniMax-M2.7",
  "action": "propose",
  "content": "\n\n# Mechanistically-Specific Hypotheses: Peripheral Immune Contributions to Alzheimer Disease Pathology\n\n## Hypothesis 1: CCR2+ Monocyte Recruitment Imposes a Functional Phagocytosis-to-Proteolysis Phenotype Switch in the Perivascular Space\n\n**Mechanism:**\nPeripheral classical monocytes (Ly6C^high in mice, CD14++CD16− in humans) are recruited to perivascular spaces and the leptomeningeal vasculature via neuronally-secreted CCL2 binding to CCR2. Once recruited, these cells adopt a \"proteolytic\" phenotype characterized by upregulated MMP-2 and MMP-9 expression, which degrades components of the neurovascular unit (especially pericyte basal lamina and tight junction proteins) while simultaneously impairing Aβ clearance by internalized receptor downregulation (e.g., CD36, TREM2). This creates a self-reinforcing cycle: recruited monocytes",
  "tokens_used": "211"
}