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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Neuroinflammation and activation of innate immunity are pathological hallmarks of Alzheimer\u2019s disease (AD). In contrast, very few studies have examined the impact of the adaptive immune system in AD pathogenesis. Here, we find that genetic ablation of peripheral immune cell populations significantly accelerates amyloid pathogenesis, worsens neuroinflammation, and alters microglial activation state. Critically, it appears that loss of IgG-producing B cells impairs microglial phagocytosis, thereby exacerbating amyloid deposition. Conversely, replacement of IgGs via direct injection or bone marrow transplantation reverses these effects and reduces A\u03b2 pathology. Together, these results highlight the importance of the adaptive immune system and its interactions with microglia in the pathogenesis of AD.<\/jats:p>","DOI":"10.1073\/pnas.1525466113","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T23:10:11Z","timestamp":1455664211000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":402,"title":["The adaptive immune system restrains Alzheimer\u2019s disease pathogenesis by modulating microglial function"],"prefix":"10.1073","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-6945","authenticated-orcid":false,"given":"Samuel E.","family":"Marsh","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA 92697;"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edsel M.","family":"Abud","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA 92697;"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alborz","family":"Karimzadeh","sequence":"additional","affiliation":[{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"},{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayk","family":"Davtyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna M.","family":"Fote","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA 92697;"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Lau","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Weinger","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"},{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Inlay","sequence":"additional","affiliation":[{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"},{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne W.","family":"Poon","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Blurton-Jones","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA 92697;"},{"name":"Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697;"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"e47","article-title":"2014 Alzheimer\u2019s disease facts and figures","volume":"10","author":"Alzheimer\u2019s Association","year":"2014","unstructured":"; 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