{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:21:16Z","timestamp":1769732476548,"version":"3.49.0"},"reference-count":124,"publisher":"Portland Press Ltd.","issue":"15","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The accumulation of extracellular amyloid-\u03b2 (A\u03b2) and intracellular hyperphosphorylated \u03c4 proteins in the brain are the hallmarks of Alzheimer\u2019s disease (AD). Much of the research into the pathogenesis of AD has focused on the amyloid or \u03c4 hypothesis. These hypotheses propose that A\u03b2 or \u03c4 aggregation is the inciting event in AD that leads to downstream neurodegeneration, inflammation, brain atrophy and cognitive impairment. Multiple drugs have been developed and are effective in preventing the accumulation and\/or clearing of A\u03b2 or \u03c4 proteins. However, clinical trials examining these therapeutic agents have failed to show efficacy in preventing or slowing the progression of the disease. Thus, there is a need for fresh perspectives and the evaluation of alternative therapeutic targets in this field. Epidemiology studies have revealed significant overlap between cardiovascular and cerebrovascular risk factors such as hypertension, diabetes, atherosclerosis and stroke to the development of cognitive impairment. This strong correlation has given birth to a renewed focus on vascular contributions to AD and related dementias. However, few genes and mechanisms have been identified. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that plays a complex role in hypertension, autoregulation of cerebral blood flow and blood\u2013brain barrier (BBB) integrity. Multiple human genome-wide association studies have linked mutations in the cytochrome P450 (CYP) 4A (CYP4A) genes that produce 20-HETE to hypertension and stroke. Most recently, genetic variants in the enzymes that produce 20-HETE have also been linked to AD in human population studies. This review examines the emerging role of 20-HETE in AD and related dementias.<\/jats:p>","DOI":"10.1042\/cs20201033","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T09:40:45Z","timestamp":1628588445000},"page":"1929-1944","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE"],"prefix":"10.1042","volume":"135","author":[{"given":"Ezekiel","family":"Gonzalez-Fernandez","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yedan","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander\u00a0P.","family":"Auchus","sequence":"additional","affiliation":[{"name":"Neurology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Fan","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-0217","authenticated-orcid":false,"given":"Richard\u00a0J.","family":"Roman","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"2021113011231001200_B1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.jalz.2016.03.001","article-title":"2016 Alzheimer\u2019s disease facts and figures","volume":"12","author":"Gaugler","year":"2016","journal-title":"Alzheimers Dement."},{"key":"2021113011231001200_B2","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1056\/NEJMsa1204629","article-title":"Monetary costs of dementia in the United States","volume":"368","author":"Hurd","year":"2013","journal-title":"N. 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