{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:55:36Z","timestamp":1791071736148,"version":"4.1.0"},"reference-count":87,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"34","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:p>\n            Increasing evidence strongly links neuroinflammation to Alzheimer\u2019s disease (AD) pathogenesis. Peripheral monocytes are crucial components of the human immune system, but their contribution to AD pathogenesis is still largely understudied partially due to limited human models. Here, we introduce human cortical organoid microphysiological systems (hCO-MPSs) to study AD monocyte-mediated neuroinflammation. By culturing doughnut-shape organoids on 3D-printed devices within standard 96-well plates, we generate hCO-MPSs with reduced necrosis, minimized hypoxia, and improved viability. Using these models, we found that monocytes from AD patients exhibit increased infiltration ability, decreased amyloid-\u03b2 clearance capacity, and stronger inflammatory response than monocytes from age-matched control donors. Moreover, we observed that AD monocytes induce pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis. Furthermore, the marked increase in\n            <jats:italic toggle=\"yes\">IL1B<\/jats:italic>\n            and\n            <jats:italic toggle=\"yes\">CCL3<\/jats:italic>\n            expression underscores their pivotal role in AD monocyte-mediated neuroinflammation. Our findings provide insight into understanding monocytes\u2019 role in AD pathogenesis, and our lab-compatible MPS models may offer a promising way for studying various neuroinflammatory diseases.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adu2708","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T17:58:56Z","timestamp":1755885536000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["Understanding monocyte-driven neuroinflammation in Alzheimer\u2019s disease using human cortical organoid microphysiological systems"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8795-8892","authenticated-orcid":true,"given":"Chunhui","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University Bloomington, IN 47405, 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