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Dementia"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (\n                      <jats:italic>TREM2<\/jats:italic>\n                      ) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The genetic association study of the R47\u00a0H\n                      <jats:italic>TREM2<\/jats:italic>\n                      variant with Alzheimer's disease (AD), neuropathology, and changes in\n                      <jats:italic>TREM2<\/jats:italic>\n                      and TYRO protein tyrosine kinase\u2010binding protein (\n                      <jats:italic>TYROBP)<\/jats:italic>\n                      gene and protein expression, and neuroinflammatory markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>TREM2<\/jats:italic>\n                      variant is associated with: (i) AD (odds ratio: 4.76;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased\n                      <jats:italic>TREM2<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.041) and\n                      <jats:italic>TYROBP<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.006) gene expression; (iv) decreased TREM2 protein levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.003) and nominal downregulation of protective markers (\u03b12\u2010macroglobulin, interleukin 4 or IL\u20104, and ApoA1) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.018).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings link the\n                      <jats:italic>TREM2<\/jats:italic>\n                      missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2014.10.013","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T18:18:16Z","timestamp":1418149096000},"page":"1163-1170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["The triggering receptor expressed on myeloid cells 2 (\n                    <i>TREM2<\/i>\n                    ) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia"],"prefix":"10.1002","volume":"11","author":[{"given":"Panos","family":"Roussos","sequence":"first","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Genetics and Genomic Science and Institute for Multiscale Biology Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Mental Illness Research, Education, and Clinical Center (VISN 3) James J. Peters VA Medical Center  Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Katsel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fam","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dushyant P.","family":"Purohit","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Pathology Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahram","family":"Haroutunian","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Mental Illness Research, Education, and Clinical Center (VISN 3) James J. 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