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Astrocytes play a key role in the neuroinflammatory environment of AD, especially through lipid metabolism regulation. However, the mechanisms by which astrocytes, particularly through the triggering receptor expressed on myeloid cells 2 (Trem2) receptor, contribute to lipid dysregulation and neuroinflammation in AD remain inadequately understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an AD mouse model and integrated single\u2010cell RNA sequencing (scRNA\u2010seq), transcriptomics, and high\u2010throughput metabolomics to analyze lipid metabolism and inflammatory profiles in astrocytes. Differential gene expression was further validated with the GEO database, and in\u00a0vitro and in\u00a0vivo experiments were conducted to assess the impact of Trem2 modulation on astrocytic inflammation and lipid composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrate that Trem2 modulates lipid metabolism in astrocytes, affecting fatty acid and phospholipid pathways. In the AD model, Trem2 expression was suppressed, enhancing nuclear factor\u2010\u03baB (NF\u2010\u03baB) signaling and promoting the secretion of pro\u2010inflammatory factors such as tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and interleukin\u20106 (IL\u20106). Trem2 overexpression reduced astrocytic inflammation and altered lipid composition, attenuating neuroinflammation both in\u00a0vitro and in\u00a0vivo. These results underscore Trem2's regulatory role in lipid metabolism and its significant impact on neuroinflammation in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies Trem2 as a pivotal regulator of astrocytic lipid metabolism and neuroinflammation in AD, providing potential molecular targets for early intervention and therapeutic strategies aimed at mitigating AD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70338","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T02:39:28Z","timestamp":1744252768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Elucidating the Role of Trem2 in Lipid Metabolism and Neuroinflammation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8865-4764","authenticated-orcid":false,"given":"Chenhui","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Northeast Agricultural University  Harbin China"},{"name":"Heilongjiang Key Laboratory of Laboratory Animals and Comparative Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Qi","sequence":"additional","affiliation":[{"name":"Suzhou Frontage New Drug Development Co., Ltd.  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