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A substantial fraction of AD risk genes converges on pathways controlling lipid metabolism and immune regulation, in which microglia serve as a central integrative hub in the brain. Although microglial phenotypes linked to different\n                    <jats:italic>APOE<\/jats:italic>\n                    genotypes have been extensively characterised, the fundamental question of how ApoE shapes the core functions of human microglia remains unresolved. Here, we generated\n                    <jats:italic>APOE<\/jats:italic>\n                    knockout (KO) microglia from AD patient\u2013derived induced pluripotent stem cells (iPSCs) and characterised their cellular and molecular phenotypes. Ablation of\n                    <jats:italic>APOE<\/jats:italic>\n                    resulted in marked lipid droplet accumulation and increased NLRP3 inflammasome activation. Transcriptomic analysis further revealed downregulation of cell cycle\u2013related pathways, accompanied by enrichment of an oxidative stress\u2013associated pathway. Consistent with these transcriptomic signatures,\n                    <jats:italic>APOE<\/jats:italic>\n                    KO microglia exhibited elevated intracellular reactive oxygen species (ROS) levels and a marked reduction in proliferative capacity. Given the importance of microglial proliferation for maintaining immune homeostasis in the brain, our findings highlight ApoE as being an important regulator of this process, with potential consequences for the pathogenesis of neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71074","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:43:08Z","timestamp":1774003388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Apolipoprotein E Deficiency Impairs Human Microglial Proliferation Accompanied by Elevated Cellular Oxidative Stress"],"prefix":"10.1111","volume":"30","author":[{"given":"Dayoung","family":"Kim","sequence":"first","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA) Kyoto University  Kyoto 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