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As a type I transmembrane receptor, TREM2 is predominantly expressed in microglia within the central nervous system. Extensive research over the past decade has consistently established the critical role of TREM2 in AD pathogenesis, encompassing its regulation of microglial inflammatory responses, amyloid-\u03b2 deposition, and tau pathology. Notably, the soluble TREM2 fragment (sTREM2) is emerging as a promising candidate biomarker for clinical progression of AD, as evidenced by human studies. Despite these advances, the precise roles of membrane-bound TREM2 and sTREM2 in AD pathogenesis remain incompletely elucidated. Novel mouse models and technological innovations have enabled therapeutic approaches targeting TREM2 for neuroprotection. This review summarizes this progress and highlights areas for future research towards the development of TREM2-directed therapeutics.\n                  <\/jats:p>","DOI":"10.1186\/s40035-025-00515-3","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T03:02:54Z","timestamp":1761879774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Roles of TREM2 in Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"14","author":[{"given":"Xiaoshan","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanping","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9116-1296","authenticated-orcid":false,"given":"Guiqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"515_CR1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s disease facts and figures 2024 Alzheimers Dement 20 3708 3821","DOI":"10.1002\/alz.13809"},{"key":"515_CR2","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1056\/NEJMoa2310168","volume":"390","author":"J Jia","year":"2024","unstructured":"Jia J, Ning Y, Chen M, Wang S, Yang H, Li F, et al. 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