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

Alzheimer's & Dementia - Tập 15 - Trang 232-244 - 2019
Kwangsik Nho1, Alexandra Kueider-Paisley2, Siamak MahmoudianDehkordi2, Matthias Arnold2,3, Shannon L. Risacher1, Gregory Louie2, Colette Blach4, Rebecca Baillie5, Xianlin Han6, Gabi Kastenmüller3,7, Wei Jia8, Guoxiang Xie8, Shahzad Ahmad9, Thomas Hankemeier10, Cornelia M. van Duijn9, John Q. Trojanowski11, Leslie M. Shaw11, Michael W. Weiner12, P. Murali Doraiswamy2,13,14, Andrew J. Saykin1
1Department of Radiology and Imaging Sciences, Center for Computational Biology and Bioinformatics, and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA
2Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
3Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
4Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
5Rosa & Co LLC, San Carlos, CA, USA
6University of Texas Health Science Center at San Antonio, San Antonio, TX USA
7German Center for Diabetes Research (DZD), Neuherberg, Germany
8University of Hawaii Cancer Center, Honolulu, HI, USA
9Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands
10Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, the Netherlands
11Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
12Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA
13Duke Institute of Brain Sciences, Duke University, Durham, NC, USA
14Department of Medicine, Duke University, Durham, NC, USA

Tóm tắt

AbstractIntroductionBile 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.MethodSerum 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).ResultsOf 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).DiscussionThis 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.

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Alzheimer's & Dementia

Tập 15

232-244

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