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Alzheimers Dement. 2018 Oct 15. pii: S1552-5260(18)33521-0. doi: 10.1016/j.jalz.2018.08.012. [Epub ahead of print]

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

Author information

1
Department 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.
2
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
3
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
4
Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
5
Rosa & Co LLC, San Carlos, CA, USA.
6
University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
7
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
8
University of Hawaii Cancer Center, Honolulu, HI, USA.
9
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
10
Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, the Netherlands.
11
Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
12
Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.
13
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke Institute of Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
14
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke Institute of Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA. Electronic address: rima.kaddurahdaouk@duke.edu.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Amyloid-β; Bile acid; Brain glucose metabolism; CSF biomarkers; Gut-liver-brain axis; MRI; Metabolomics; PET

PMID:
30337152
DOI:
10.1016/j.jalz.2018.08.012

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