Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

Published

Journal Article

INTRODUCTION: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. 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). METHODS: 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-related genetic variants, adjusting for confounders and multiple testing. RESULTS: 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 7α-dehydroxylation 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-related genes implicated in AD showed associations with BA profiles. DISCUSSION: 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-liver-brain axis in the pathogenesis of AD.

Full Text

Duke Authors

Cited Authors

  • MahmoudianDehkordi, S; Arnold, M; Nho, K; Ahmad, S; Jia, W; Xie, G; Louie, G; Kueider-Paisley, A; Moseley, MA; Thompson, JW; St John Williams, L; Tenenbaum, JD; Blach, C; Baillie, R; Han, X; Bhattacharyya, S; Toledo, JB; Schafferer, S; Klein, S; Koal, T; Risacher, SL; Kling, MA; Motsinger-Reif, A; Rotroff, DM; Jack, J; Hankemeier, T; Bennett, DA; De Jager, PL; Trojanowski, JQ; Shaw, LM; Weiner, MW; Doraiswamy, PM; van Duijn, CM; Saykin, AJ; Kastenmüller, G; Kaddurah-Daouk, R; Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium,

Published Date

  • January 2019

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 76 - 92

PubMed ID

  • 30337151

Pubmed Central ID

  • 30337151

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2018.07.217

Language

  • eng

Conference Location

  • United States