TY - JOUR
T1 - Altered bile acid profile in mild cognitive impairment and Alzheimer's disease
T2 - Relationship to neuroimaging and CSF biomarkers
AU - Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
AU - Nho, Kwangsik
AU - Kueider-Paisley, Alexandra
AU - MahmoudianDehkordi, Siamak
AU - Arnold, Matthias
AU - Risacher, Shannon L.
AU - Louie, Gregory
AU - Blach, Colette
AU - Baillie, Rebecca
AU - Han, Xianlin
AU - Kastenmüller, Gabi
AU - Jia, Wei
AU - Xie, Guoxiang
AU - Ahmad, Shahzad
AU - Hankemeier, Thomas
AU - van Duijn, Cornelia M.
AU - Trojanowski, John Q.
AU - Shaw, Leslie M.
AU - Weiner, Michael W.
AU - Doraiswamy, P. Murali
AU - Saykin, Andrew J.
AU - Kaddurah-Daouk, Rima
N1 - Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
N2 - 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 ([ 18 F]FDG PET). Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ 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.
AB - 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 ([ 18 F]FDG PET). Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ 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.
KW - Alzheimer's disease
KW - Amyloid-β
KW - Bile acid
KW - Brain glucose metabolism
KW - CSF biomarkers
KW - Gut-liver-brain axis
KW - MRI
KW - Metabolomics
KW - PET
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U2 - 10.1016/j.jalz.2018.08.012
DO - 10.1016/j.jalz.2018.08.012
M3 - Article
C2 - 30337152
AN - SCOPUS:85060999700
SN - 1552-5260
VL - 15
SP - 232
EP - 244
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 2
ER -