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Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers
- Nho, Kwangsik;
- Kueider‐Paisley, Alexandra;
- MahmoudianDehkordi, Siamak;
- Arnold, Matthias;
- Risacher, Shannon L;
- Louie, Gregory;
- Blach, Colette;
- Baillie, Rebecca;
- Han, Xianlin;
- Kastenmüller, Gabi;
- Jia, Wei;
- Xie, Guoxiang;
- Ahmad, Shahzad;
- Hankemeier, Thomas;
- van Duijn, Cornelia M;
- Trojanowski, John Q;
- Shaw, Leslie M;
- Weiner, Michael W;
- Doraiswamy, P Murali;
- Saykin, Andrew J;
- Kaddurah‐Daouk, Rima;
- Consortium, for the Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics
Published Web Location
https://doi.org/10.1016/j.jalz.2018.08.012Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.