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-b deposition. Method: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n 5 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 Ab1-42 (“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.

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Keywords Metabolomics, Bile acid, Alzheimer’s disease, Amyloid-b, CSF biomarkers, Brain glucose metabolism, PET, MRI, Gut-liver-brain axis
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Journal Alzheimer's & Dementia
Nho, K, Kueider-Paisley, A., MahmoudianDehkordi, S., Arnold, M., Risacher, S.L, Louie, G., … Fernández, D. (2019). Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers. Alzheimer's & Dementia, 15(2), 232–244. doi:10.1016/j.jalz.2018.08.012