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Here, we establish a modular human forebrain organoid platform that systematically integrates human induced pluripotent stem cell-derived microglia and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to reconstitute multicellular AD pathology. This system enables functional interrogation of both innate and adaptive immune components in a human-relevant context. Using this platform, we demonstrate that microglia mediate amyloid-\u03b2 clearance and neuronal maturation but also drive inflammatory activation and recruit CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells through CCL4\/5 signaling via CCR1\/5 and CXCR3, establishing a neuroinflammatory feedback loop. Pharmacological targeting of CCR5 or CXCR3 blocks T cell recruitment and modulates autophagy in a microglia-dependent manner. This modular organoid platform provides a versatile tool for dissecting neuron\u2013immune interactions and enables cell-type-specific therapeutic screening in human neuroinflammatory disease models.\n                  <\/jats:p>","DOI":"10.7554\/elife.111730","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:39:52Z","timestamp":1785940792000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.111730","source":"Crossref","is-referenced-by-count":0,"title":["An integrated human forebrain organoid reveals microglia-mediated CD8+ T cell recruitment and neuroimmune dysfunction in Alzheimer\u2019s disease pathology"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-339X","authenticated-orcid":true,"given":"Yilin","family":"Feng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biopharmaceutical and Health Engineering 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