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Nho, K.* ; Kueider-Paisley, A.* ; MahmoudianDehkordi, S.* ; Arnold, M. ; Risacher, S.L.* ; Louie, G.* ; Blach, C.* ; Baillie, R.A.* ; Han, X.* ; Kastenmüller, G. ; Jia, W.* ; Xie, G.* ; Ahmad, S.* ; Hankemeier, T.* ; van Duijn, C.M.* ; Trojanowski, J.Q.* ; Shaw, L.M.* ; Weiner, M.W.* ; Doraiswamy, P.M.* ; Saykin, A.J.* ; Kaddurah-Daouk, R.*

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

Alzheimers Dement. 15, 232-244 (2019)

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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-beta 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 ([F-18]FDG PET).Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSFA beta(1-42) ("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. (C) 2018 Published by Elsevier Inc. on behalf of the Alzheimer's Association.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Metabolomics ; Bile Acid ; Alzheimer's Disease ; Amyloid-beta ; Csf Biomarkers ; Brain Glucose Metabolism ; Pet ; Mri ; Gut-liver-brain Axis; Isolated Rat Hepatocytes; Surface-based Analysis; Gut-brain Axis; Cerebrospinal-fluid; Cholesterol-metabolism; Ursodeoxycholic Acid; Oxidative Stress; Random-field; Vitamin-d; Fdg-pet

ISSN (print) / ISBN 1552-5260

e-ISSN 1552-5279

Journal Alzheimer's & Dementia

Quellenangaben Volume: 15, Issue: 2, Pages: 232-244

Publisher Elsevier

Publishing Place New York, NY [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)