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Rare TREM2 variants that affect TREM2 function lead to an increased risk of developing AD. In murine models of AD, TREM2 deficiency prevents microglial clustering around A\u03b2 deposits. However, the origin of myeloid cells surrounding amyloid and the impact of TREM2 on A\u03b2 accumulation are a matter of debate. Using parabiosis, we found that amyloid-associated myeloid cells derive from brain-resident microglia rather than from recruitment of peripheral blood monocytes. To determine the impact of TREM2 deficiency on A\u03b2 accumulation, we examined A\u03b2 plaques in the 5XFAD model of AD at the onset of A\u03b2-related pathology. At this early time point, A\u03b2 accumulation was similar in TREM2-deficient and -sufficient 5XFAD mice. However, in the absence of TREM2, A\u03b2 plaques were not fully enclosed by microglia; they were more diffuse, less dense, and were associated with significantly greater neuritic damage. Thus, TREM2 protects from AD by enabling microglia to surround and alter A\u03b2 plaque structure, thereby limiting neuritic damage.<\/jats:p>","DOI":"10.1084\/jem.20151948","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T10:12:27Z","timestamp":1460974347000},"page":"667-675","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":776,"title":["TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques"],"prefix":"10.1084","volume":"213","author":[{"given":"Yaming","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 1"},{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler K.","family":"Ulland","sequence":"additional","affiliation":[{"name":"Department of 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