Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.

Journal Article (Journal Article)

INTRODUCTION: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition. METHOD: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET). RESULTS: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1-42 ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05). DISCUSSION: This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.

Full Text

Duke Authors

Cited Authors

  • Nho, K; Kueider-Paisley, A; MahmoudianDehkordi, S; Arnold, M; Risacher, SL; Louie, G; Blach, C; Baillie, R; Han, X; Kastenmüller, G; Jia, W; Xie, G; Ahmad, S; Hankemeier, T; van Duijn, CM; Trojanowski, JQ; Shaw, LM; Weiner, MW; Doraiswamy, PM; Saykin, AJ; Kaddurah-Daouk, R; Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium,

Published Date

  • February 2019

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 232 - 244

PubMed ID

  • 30337152

Pubmed Central ID

  • PMC6454538

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2018.08.012


  • eng

Conference Location

  • United States