{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:23:32Z","timestamp":1793917412485,"version":"4.8.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is increasingly recognized as a disorder of innate immune dysregulation within the central nervous system. The triggering receptor expressed on myeloid cells 2 (TREM2), a microglial immunoreceptor, has emerged as a pivotal genetic risk factor for late-onset AD, underscoring the critical role of neuroimmune interactions in disease pathogenesis. This review synthesizes recent advances concerning TREM2\u2019s modulation of core microglial functions, including phagocytosis, inflammatory signaling, cellular metabolism, and survival, processes that are essential for responding to amyloid-\u03b2 plaques and neuronal damage. We highlight the TREM2-APOE pathway as a central mechanism driving the disease-associated microglia (DAM) phenotype and examine how loss-of-function mutations such as\n                    <jats:italic>R47H<\/jats:italic>\n                    disrupt immune surveillance, aggravate amyloid pathology, and promote neuroinflammation. Additionally, we explore the diagnostic and therapeutic potential of soluble TREM2 (sTREM2) and TREM2-targeted immunotherapies, which enhance plaque encapsulation and cognitive outcomes in preclinical models. By integrating genetic, molecular, and clinical evidence, this review establishes TREM2 as a keystone regulator linking amyloidosis, tauopathy, and neuroinflammation, highlighting its promise as a target for disease-modifying therapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1739875","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:56Z","timestamp":1771392836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["TREM2 and microglial immunity in Alzheimer\u2019s disease: mechanisms, genetics, and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Tianqing","family":"Wang","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"Graduate School of Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhou","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638","article-title":"2022 Alzheimer\u2019s disease facts and figures","volume":"18","year":"2022","journal-title":"Alzheimers Dement"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.7","article-title":"TREM2 variants: new keys to decipher Alzheimer disease pathogenesis","volume":"17","author":"Colonna","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1086\/342259","article-title":"Mutations in two genes encoding different subunits of a receptor signaling complex result in 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