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The elevated serum bile acids may be the result of hepatic peroxisomal dysfunction. Circulating hydrophobic bile acids are able to disrupt the blood-brain barrier and promote the formation of amyloid-\u03b2 plaques through enhancing the oxidation of docosahexaenoic acid. Hydrophobic bile acid may find their ways into the neurons via the apical sodium-dependent bile acid transporter. It has been shown that hydrophobic bile acids impose their pathological effects by activating farnesoid X receptor and suppressing bile acid synthesis in the brain, blocking NMDA receptors, lowering brain oxysterol levels, and interfering with 17\u03b2-estradiol actions such as LCA by binding to E2 receptors (molecular modelling data exclusive to this paper). Hydrophobic bile acids may interfere with the sonic hedgehog signaling through alteration of cell membrane rafts and reducing brain 24(S)-hydroxycholesterol. This article will 1) analyze the pathological roles of circulating hydrophobic bile acids in the brain, 2) propose therapeutic approaches, and 3) conclude that consideration be given to reducing\/monitoring toxic bile acid levels in patients with AD or aMCI, prior\/in combination with other treatments.<\/jats:p>","DOI":"10.3233\/adr-220071","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T11:47:11Z","timestamp":1676634431000},"page":"173-211","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer\u2019s           Disease"],"prefix":"10.1177","volume":"7","author":[{"given":"Touraj","family":"Ehtezazi","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences,\r            Liverpool John Moores University, Liverpool,\r            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