{"title":"Decoding microglial functions in Alzheimer's disease: insights from human models.","authors":"Chandrika Rao, Stefan Semrau, Valentina Fossati","doi":"10.1016/j.it.2025.02.011","DOIUrl":null,"url":null,"abstract":"<p><p>Microglia, key orchestrators of the brain's immune responses, play a pivotal role in the progression of Alzheimer's disease (AD). Emerging human models, including stem cell-derived microglia and cerebral organoids, are transforming our understanding of microglial contributions to AD pathology. In this review, we highlight how these models have uncovered human-specific microglial responses to amyloid plaques and their regulation of neuroinflammation, which are not recapitulated in animal models. We also illustrate how advanced human models that better mimic brain physiology and AD pathology are providing unprecedented insights into the multifaceted roles of microglia. These innovative approaches, combined with sophisticated technologies for cell editing and analysis, are shaping AD research and opening new avenues for therapeutic interventions targeting microglia.</p>","PeriodicalId":54412,"journal":{"name":"Trends in Immunology","volume":" ","pages":"310-323"},"PeriodicalIF":13.9000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993344/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.it.2025.02.011","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Microglia, key orchestrators of the brain's immune responses, play a pivotal role in the progression of Alzheimer's disease (AD). Emerging human models, including stem cell-derived microglia and cerebral organoids, are transforming our understanding of microglial contributions to AD pathology. In this review, we highlight how these models have uncovered human-specific microglial responses to amyloid plaques and their regulation of neuroinflammation, which are not recapitulated in animal models. We also illustrate how advanced human models that better mimic brain physiology and AD pathology are providing unprecedented insights into the multifaceted roles of microglia. These innovative approaches, combined with sophisticated technologies for cell editing and analysis, are shaping AD research and opening new avenues for therapeutic interventions targeting microglia.
期刊介绍：
Trends in Immunology serves as a vital platform for tracking advancements across various areas of immunology, offering concise reviews and hypothesis-driven viewpoints in each issue. With additional sections providing comprehensive coverage, the journal offers a holistic view of immunology. This broad perspective makes it an invaluable resource for researchers, educators, and students, facilitating the connection between basic and clinical immunology. Recognized as one of the top monthly review journals in its field, Trends in Immunology is highly regarded by the scientific community.
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