Nho, KwangsikKueider-Paisley, AlexandraMahmoudianDehkordi, SiamakArnold, MatthiasRisacher, Shannon L.Louie, GregoryBlach, ColetteBaillie, RebeccaHan, XianlinKastenmüller, GabiJia, WeiXie, GuoxiangAhmad, ShahzadHankemeier, Thomasvan Duijn, Cornelia M.Trojanowski, John Q.Shaw, Leslie M.Weiner, Michael W.Doraiswamy, P. MuraliSaykin, Andrew J.Kaddurah-Daouk, Rima2019-08-022019-08-022019-02Nho, K., Kueider-Paisley, A., MahmoudianDehkordi, S., Arnold, M., Risacher, S. L., Louie, G., … Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium (2019). Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers. Alzheimer's & dementia : the journal of the Alzheimer's Association, 15(2), 232–244. doi:10.1016/j.jalz.2018.08.012https://hdl.handle.net/1805/20149INTRODUCTION: 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.en-USPublisher PolicyAlzheimer's diseaseAmyloid-βBile acidBrain glucose metabolismCSF biomarkersGut-liver-brain axisMRIMetabolomicsPETArticle