An integrated human forebrain organoid reveals microglia-mediated CD8(+) T cell recruitment and neuroimmune dysfunction in Alzheimer's disease pathology.

Microglia in human forebrain organoids mediate amyloid-β clearance, recruit CD8+ T cells via CCL4/5 signaling, and establish a neuroinflammatory feedback loop in Alzheimer’s disease models.

• Why it matters: Understanding the neuroimmune mechanisms in Alzheimer’s disease is crucial because immune dysfunction is genetically implicated but remains poorly characterized in human tissue, hindering targeted therapies.
• What they did: A modular human forebrain organoid platform was developed that integrates microglia and CD8+ T cells, allowing functional analysis of innate and adaptive immune responses in a human-relevant system.
• The result: Pharmacological blockade of CCR5 or CXCR3 inhibits T cell recruitment and modulates autophagy in a microglia-dependent manner, offering potential therapeutic avenues for neuroinflammatory conditions.