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Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD\u2010related genetic variants, adjusting for confounders and multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7\u03b1\u2010dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response\u2013related genes implicated in AD showed associations with BA profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut\u2010liver\u2010brain axis in the pathogenesis of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2018.07.217","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T05:05:49Z","timestamp":1539579949000},"page":"76-92","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":688,"title":["Altered bile acid profile associates with cognitive impairment in Alzheimer's disease\u2014An emerging role for gut microbiome"],"prefix":"10.1002","volume":"15","author":[{"given":"Siamak","family":"MahmoudianDehkordi","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University Durham NC USA"},{"name":"Institute of Bioinformatics and Systems Biology Helmholtz Zentrum M\u00fcnchen German Research Center for Environmental Health Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangsik","family":"Nho","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahzad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Centre Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jia","sequence":"additional","affiliation":[{"name":"University of Hawaii Cancer Center Honolulu HI USA"},{"name":"Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Xie","sequence":"additional","affiliation":[{"name":"University of Hawaii Cancer Center Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Louie","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kueider\u2010Paisley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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