{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T11:14:07Z","timestamp":1794222847238,"version":"4.8.0"},"reference-count":141,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute of Aging of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG072896"],"award-info":[{"award-number":["R01AG072896"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute of Aging of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG062840"],"award-info":[{"award-number":["R01AG062840"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can modulate cerebral AD pathology include Toll-like receptors, protein kinase-B (Akt)\/mammalian target of rapamycin (mTOR) pathway, cyclic adenosine monophosphate (cAMP) response element-binding protein phosphorylation pathway, glycogen synthase kinase 3-\u03b2, cyclin-dependent kinase-5, insulin-like growth factor type-1 receptor, modulation of \u03b2-amyloid (A\u03b2) synthesis and clearance, microglial mediated, and brain endothelial alterations. Besides these brain-centric pathways, alcohol-mediated liver injury may significantly affect brain A\u03b2 levels through alterations in the peripheral-to-central A\u03b2 homeostasis. This article reviews published experimental studies (cell culture and AD rodent models) to summarize the scientific evidence and probable mechanisms (both cerebral and hepatic) by which alcohol promotes or protects against AD progression.<\/jats:p>","DOI":"10.3390\/ijms24119492","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T04:40:51Z","timestamp":1685508051000},"page":"9492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Alcohol as a Modifiable Risk Factor for Alzheimer\u2019s Disease\u2014Evidence from Experimental Studies"],"prefix":"10.3390","volume":"24","author":[{"given":"Devaraj V.","family":"Chandrashekar","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3530-2557","authenticated-orcid":false,"given":"Ross A.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derick","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7459-0723","authenticated-orcid":false,"given":"Rachita K.","family":"Sumbria","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA 92618, USA"},{"name":"Department of Neurology, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2022). 2022 Alzheimer\u2019s disease facts and figures. 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