{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:41:52Z","timestamp":1784673712545,"version":"3.55.0"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. Neuroinflammation drives AD progression and therefore represents a promising target for diagnosis and therapy. In early AD, microglia polarize into pro-inflammatory and anti-inflammatory cellular subgroups that mediate the initial immune response, yet the regulatory relationships between these microglial subgroups remain poorly understood. In this study, we investigated the interplay between pro- and anti-inflammatory microglial subgroups from multiple perspectives. Comparative transcriptomics and bioinformatics analyses implicated the Trem2 signaling pathway in an anti-inflammatory microglial subgroup. Fluorescence-activated cell sorting (FACS) and gene regulation analysis indicated that microglial subgrouping and microgliosis preceded cytokine upregulation during early amyloid pathology. Further immunoassays revealed that anti-inflammatory Neurodegeneration-Related Modules and pro-inflammatory microglial subgroups, Interferon-Related Modules and LPS-Related Modules, were co-regulated by shared upstream pro-inflammatory regulators. Such co-regulation of heterogeneous microglial subgroups may balance microglial activation and promote the development of AD chronic neuroinflammation. In summary, our study uncovered previously overlooked co-regulation of microglial subgroups in AD and provides a systems biology framework that may inform improved diagnostic markers and immunotherapeutic strategies.<\/jats:p>","DOI":"10.1371\/journal.pone.0337741","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:25:24Z","timestamp":1764959124000},"page":"e0337741","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Co-regulation of microglial subgroups in Alzheimer\u2019s amyloid pathology: Implications for diagnosis and drug 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