Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.
Abstract
INTRODUCTION:Increasing evidence suggests a role for the gut microbiome in central
nervous system disorders and a specific role for the gut-brain axis in neurodegeneration.
Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in
the liver and are further metabolized by gut bacteria. They have major regulatory
and signaling functions and seem dysregulated in Alzheimer's disease (AD). METHODS:Serum
levels of 15 primary and secondary BAs and their conjugated forms were measured in
1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive
impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in
the AD Neuroimaging Initiative. We assessed associations of BA profiles including
selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting
for confounders and multiple testing. RESULTS:In AD compared to cognitively normal
older adults, we observed significantly lower serum concentrations of a primary BA
(cholic acid [CA]) and increased levels of the bacterially produced, secondary BA,
deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio
of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly
associated with cognitive decline, a finding replicated in serum and brain samples
in the Rush Religious Orders and Memory and Aging Project. Several genetic variants
in immune response-related genes implicated in AD showed associations with BA profiles.
DISCUSSION:We report for the first time an association between altered BA profile,
genetic variants implicated in AD, and cognitive changes in disease using a large
multicenter study. These findings warrant further investigation of gut dysbiosis and
possible role of gut-liver-brain axis in the pathogenesis of AD.
Type
Journal articleSubject
Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics
ConsortiumPermalink
https://hdl.handle.net/10161/17842Published Version (Please cite this version)
10.1016/j.jalz.2018.07.217Publication Info
MahmoudianDehkordi, Siamak; Arnold, Matthias; Nho, Kwangsik; Ahmad, Shahzad; Jia,
Wei; Xie, Guoxiang; ... Alzheimer's Disease Neuroimaging Initiative and the Alzheimer
Disease Metabolomics Consortium (2018). Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An
emerging role for gut microbiome. Alzheimer's & dementia : the journal of the Alzheimer's Association. 10.1016/j.jalz.2018.07.217. Retrieved from https://hdl.handle.net/10161/17842.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Matthias Arnold
Adjunct Associate Professor in the Department of Psychiatry and Behavioral Sciences
P. Murali Doraiswamy
Professor of Psychiatry and Behavioral Sciences
Murali Doraiswamy MBBS FRCP is Professor of Psychiatry and Professor in Medicine at
Duke University School of Medicine where he is a highly cited physician scientist
at the Duke Institute for Brain Sciences. He is also a Senior Fellow at the Duke
Center for the Study of Aging and an Affiliate Faculty at the Duke Center for Precision
Medicine and Applied Genomics as well as the Duke Microbiome Center. He directs a
clinical trials unit that has been involved in the development of ma
Rima Fathi Kaddurah-Daouk
Professor in Psychiatry and Behavioral Sciences
Overall Research Goals:
My research interest over the past decade has focused on scaling up biochemical knowledge
for gaining a deeper understanding of the molecular basis of neurodegenerative and
neuropsychiatric disorders and finding ways to optimize their treatment. I have also
made seminal contributions to the development of the metabolomics field and applications
of metabolomics for the study of drug effects, establishing foundations for “Pharmacometabolomi
Martin Arthur Moseley III
Adjunct Professor in the Department of Cell Biology
Jessica Dale Tenenbaum
Associate Professor of Biostatistics & Bioinformatics
Dr. Tenenbaum is a faculty member in the Division of Translational Biomedical Informatics
in the Department of Biostatistics and Bioinformatics. Her primary research interests
are 1. Informatics to enable precision medicine; 2. Mental health informatics; 3.
Infrastructure and standards to enable research collaboration and integrative data
analysis; and 4. Ethical, legal, and social issues that arise in translational research,
direct to consumer genetic testing, and data sharing. Cu
J. Will Thompson
Adjunct Assistant Professor in the Department of Pharmacology & Cancer Biology
Dr. Thompson's research focuses on the development and deployment of proteomics and
metabolomics mass spectrometry techniques for the analysis of biological systems.
He served as the Assistant Director of the Proteomics and Metabolomics Shared Resource
in the Duke School of Medicine from 2007-2021. He currently maintains collaborations
in metabolomics and proteomics research at Duke, and develops new tools for chemical
analysis as a Princi
Alphabetical list of authors with Scholars@Duke profiles.

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