期刊
ALZHEIMERS & DEMENTIA
卷 15, 期 2, 页码 232-244出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2018.08.012
关键词
Metabolomics; Bile acid; Alzheimer's disease; Amyloid-beta; CSF biomarkers; Brain glucose metabolism; PET; MRI; Gut-liver-brain axis
资金
- National Institute on Aging component of the Accelerated Medicines Partnership for AD (AMP-AD) Target Discovery and Preclinical Validation Project [R01AG046171]
- National Institute of Biomedical Imaging and Bioengineering [R01EB022574]
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- Fujirebio
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Merck Co., Inc.
- Meso Scale Diagnostics
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- NIA [U01AG024904-09S4, P50NS053488, R01AG19771, P30AG10133, P30AG10124, R03AG054936, K01AG049050]
- National Library of Medicine [R01LM011360, R01LM012535, R00LM011384]
- Helmholtz Zentrum
- Indiana Clinical and Translational Science Institute
- Indiana University-IU Health Strategic Neuroscience Research Initiative
- National Institute on Aging a component of the M2OVE-AD Consortium (Molecular Mechanisms of the Vascular Etiology of AD-Consortium) [RF1 AG0151550]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-20012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- BioClinica, Inc.
- EuroImmun
- F. Hoffmann La Roche Ltd
- Genentech, Inc.
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Lumosity
- Lundbeck
- Meso Scale Diagnostics, LLC.
- Neurotrack Technologies
- Servier
- Transition Therapeutics
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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