Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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: CSF biomarkers, atrophy (MRI), and brain glucose metabolism ([ 18 F]FDG-PET). Results Of 23 BA and relevant calculated ratios, three BA signatures were associated with CSF Aβ1-42 (“A”) and three with CSF p-tau181 (“T”) (corrected p <0.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (“N”), respectively (corrected p <0.05). Conclusion 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.

Original publication

DOI

10.1101/284141

Type

Journal article

Publication Date

18/03/2018

Keywords

for the Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium