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

Journal article

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.

Authors: Nho, K; Kueider-Paisley, A; Mahmoudian-Dehkordi, S; Arnold, M; Risacher, SL

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Alzheimer's and Dementia
• Volume: 15
• Issue: 2
• Pages: 232-244
• Publication date: 2018-10-15
• Acceptance date: 2018-08-21
• DOI: 10.1016/j.jalz.2018.08.012
• EISSN: 1552-5279
• ISSN: 1552-5260
• Pmid: 30337152
• Language: English
• Keywords: FFR