{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:34:04Z","timestamp":1791419644830,"version":"4.3.3"},"reference-count":32,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,3,9]]},"abstract":"<jats:p>Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer\u2019s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2\u2019s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.<\/jats:p>","DOI":"10.1084\/jem.20142322","type":"journal-article","created":{"date-parts":[[2015,3,2]],"date-time":"2015-03-02T22:22:38Z","timestamp":1425334958000},"page":"287-295","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":642,"title":["TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer\u2019s disease mouse models"],"prefix":"10.1084","volume":"212","author":[{"given":"Taylor R.","family":"Jay","sequence":"first","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"},{"name":"Case Western Reserve University, Cleveland, OH 44106 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal M.","family":"Miller","sequence":"additional","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"},{"name":"Case Western Reserve University, Cleveland, OH 44106 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah C.","family":"Graham","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Bemiller","sequence":"additional","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"},{"name":"Kent State University, Kent, OH 44340 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"Broihier","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, OH 44106 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixiang","family":"Xu","sequence":"additional","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Margevicius","sequence":"additional","affiliation":[{"name":"The Lerner Research Institute 1 and 2"},{"name":"Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH 44195 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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