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One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared neuronal genes upregulated by estrogen in ovariectomized female rhesus macaques with a database of &gt;17,000 diverse gene sets and applied a rare variant burden test to exome sequencing data from 1208 female AD patients with the age of onset &lt; 75 years and 2162 female AD controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found a striking overlap between genes upregulated by estrogen in macaques and genes downregulated in the human postmortem AD brain, and we found that estrogen upregulates the\n                      <jats:italic>APOE<\/jats:italic>\n                      gene and that progesterone acts antagonistically to estrogen genome\u2010wide. We also found that female patients with AD have excess rare mutations in the early menopause gene\n                      <jats:italic>MCM8<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We show with genomic data that the menopausal loss of estrogen could underlie the increased risk for AD in women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.trci.2019.09.004","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T20:35:43Z","timestamp":1575923743000},"page":"906-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Estrogen activates Alzheimer's disease genes"],"prefix":"10.1002","volume":"5","author":[{"given":"Abhirami","family":"Ratnakumar","sequence":"first","affiliation":[{"name":"Department of Systems and Computational Biology Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel E.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Systems and Computational Biology Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryen A.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Dominick P. 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