{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:00:44Z","timestamp":1791813644451,"version":"4.3.4"},"reference-count":144,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":144,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia affecting almost 50 million people worldwide. The \u03b54 allele of Apolipoprotein E (APOE) is the strongest known genetic risk factor for late-onset AD cases, with homozygous APOE4 carriers being approximately 15-times more likely to develop the disease. With 25% of the population being APOE4 carriers, understanding the role of this allele in AD pathogenesis and pathophysiology is crucial. Though the exact mechanism by which \u03b54 allele increases the risk for AD is unknown, the processes mediated by APOE, including cholesterol transport, synapse formation, modulation of neurite outgrowth, synaptic plasticity, destabilization of microtubules, and \u03b2-amyloid clearance, suggest potential therapeutic targets. This review will summarize the impact of APOE on neurons and neuronal signaling, the interactions between APOE and AD pathology, and the association with memory decline. We will then describe current treatments targeting APOE4, complications associated with the current therapies, and suggestions for future areas of research and treatment.<\/jats:p>","DOI":"10.1042\/ns20180203","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T16:19:41Z","timestamp":1554740381000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["The role of APOE4 in Alzheimer\u2019s disease: strategies for future therapeutic interventions"],"prefix":"10.1042","volume":"3","author":[{"given":"Holly\u00a0C.","family":"Hunsberger","sequence":"first","affiliation":[{"name":"Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc. (RFMH)\/New York State Psychiatric Institute (NYSPI), New York, NY 10032, U.S.A."},{"name":"Department of Psychiatry, Columbia University, New York, NY 10032, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka\u00a0D.","family":"Pinky","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn, AL 36849, U.S.A."},{"name":"Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn, AL 36849, U.S.A."},{"name":"Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu","family":"Suppiramaniam","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn, AL 36849, U.S.A."},{"name":"Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8465-5594","authenticated-orcid":false,"given":"Miranda\u00a0N.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn, AL 36849, U.S.A."},{"name":"Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,4,18]]},"reference":[{"key":"2021111608023379300_B1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jalz.2018.02.001","article-title":"2018 Alzheimer\u2019s disease facts and figures","volume":"14","author":"Alzheimer\u2019s Association","year":"2018","journal-title":"Alzheimers Dement."},{"key":"2021111608023379300_B2","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement."},{"key":"2021111608023379300_B3","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"2021111608023379300_B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0006-291X(74)90882-1","article-title":"An apolipoprotein preferentially enriched in cholesteryl ester-rich very low density lipoproteins","volume":"58","author":"Shore","year":"1974","journal-title":"Biochem. 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