{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:17:49Z","timestamp":1791555469670,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01 AG046170"],"award-info":[{"award-number":["U01 AG046170"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG057907"],"award-info":[{"award-number":["R01 AG057907"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Microglial TYROBP (DAP12) is a network hub and driver in sporadic late\u2010onset Alzheimer's disease (AD). TYROBP is a cytoplasmic adaptor for TREM2 and other receptors, but little is known about its roles and actions in AD. Herein, we demonstrate that endogenous\n                      <jats:italic>Tyrobp<\/jats:italic>\n                      transcription is specifically increased in recruited microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a novel transgenic mouse overexpressing TYROBP in microglia, we observed a decrease of the amyloid burden and an increase of TAU phosphorylation stoichiometry when crossed with\n                      <jats:italic>APP\/PSEN1<\/jats:italic>\n                      or\n                      <jats:italic>\n                        MAPT\n                        <jats:sup>P301S<\/jats:sup>\n                      <\/jats:italic>\n                      mice, respectively. Characterization of these mice revealed\n                      <jats:italic>Tyrobp<\/jats:italic>\n                      \u2010related modulation of apolipoprotein E (\n                      <jats:italic>Apoe<\/jats:italic>\n                      ) transcription. We also showed that\n                      <jats:italic>Tyrobp<\/jats:italic>\n                      and\n                      <jats:italic>Apoe<\/jats:italic>\n                      mRNAs were increased in\n                      <jats:italic>Trem2<\/jats:italic>\n                      \u2010null microglia recruited around either amyloid beta deposits or a cortical stab injury. Conversely, microglial\n                      <jats:italic>Apoe<\/jats:italic>\n                      transcription was dramatically diminished when\n                      <jats:italic>Tyrobp<\/jats:italic>\n                      was absent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results provide evidence that TYROBP\u2010APOE signaling does not require TREM2 and could be an initiating step in establishment of the\n                      <jats:styled-content>d<\/jats:styled-content>\n                      isease\u2010\n                      <jats:styled-content>a<\/jats:styled-content>\n                      ssociated\n                      <jats:styled-content>m<\/jats:styled-content>\n                      icroglia (DAM) phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12256","type":"journal-article","created":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T13:45:08Z","timestamp":1607780708000},"page":"149-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Reactive or transgenic increase in microglial TYROBP reveals a TREM2\u2010independent TYROBP\u2013APOE link in wild\u2010type and Alzheimer's\u2010related mice"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-7380","authenticated-orcid":false,"given":"Mickael","family":"Audrain","sequence":"first","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-9666","authenticated-orcid":false,"given":"Jean\u2010Vianney","family":"Haure\u2010Mirande","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Mleczko","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences and Icahn Institute of Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"St George\u2010Hyslop","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fraser","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences and Icahn Institute of Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-4721","authenticated-orcid":false,"given":"Sam","family":"Gandy","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"National Institute on Aging\u2010Designated Alzheimer's Disease Research Center and Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Research and Development James J. 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