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In this review, we consider this topic from a female perspective with a specific focus on how women's vulnerability to the disease is affected by the individual and interactive effects of estrogens and apolipoprotein E (\n                    <jats:italic>APOE<\/jats:italic>\n                    ) genotype. Importantly,\n                    <jats:italic>APOE<\/jats:italic>\n                    appears to modulate systemic and neural outcomes of both menopause and estrogen\u2010based hormone therapy. In the brain, dementia risk is greater in\n                    <jats:italic>APOE4<\/jats:italic>\n                    carriers, and the impacts of hormone therapy on cognitive decline and dementia risk vary according to both outcome measure and\n                    <jats:italic>APOE<\/jats:italic>\n                    genotype. Beyond the CNS, estrogen and\n                    <jats:italic>APOE<\/jats:italic>\n                    genotype affect vulnerability to menopause\u2010associated bone loss, dyslipidemia and cardiovascular disease risk. An emerging concept that may link these relationships is the possibility that the effects of\n                    <jats:italic>APOE<\/jats:italic>\n                    in women interact with estrogen status by mechanisms that may include modulation of estrogen responsiveness. This review highlights the need to consider the key AD risk factors of advancing age in a sex\u2010specific manner to optimize development of therapeutic approaches for AD, a view aligned with the principle of personalized medicine.\n                  <\/jats:p>","DOI":"10.1111\/jne.13209","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T11:18:56Z","timestamp":1666264736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Role of estrogen in women's Alzheimer's disease risk as modified by\n                    <scp>\n                      <i>APOE<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"35","author":[{"given":"Ana C.","family":"Valencia\u2010Olvera","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Maldonado Weng","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Christensen","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"LaDu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-7668","authenticated-orcid":false,"given":"Christian J.","family":"Pike","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0843-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.02.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1255"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2011.088"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.10.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510410028015"},{"issue":"16","key":"e_1_2_10_8_1","first-page":"1349","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. 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