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Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers
Author(s) -
Nho Kwangsik,
KueiderPaisley Alexandra,
MahmoudianDehkordi Siamak,
Arnold Matthias,
Risacher Shan L.,
Louie Gregory,
Blach Colette,
Baillie Rebecca,
Han Xianlin,
Kastenmüller Gabi,
Jia Wei,
Xie Guoxiang,
Ahmad Shahzad,
Hankemeier Thomas,
Duijn Cornelia M.,
Trojanowski John Q.,
Shaw Leslie M.,
Weiner Michael W.,
Doraiswamy P. Murali,
Saykin Andrew J.,
KaddurahDaouk Rima
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.08.012
Subject(s) - cerebrospinal fluid , neuroimaging , atrophy , neurodegeneration , neuroinflammation , medicine , alzheimer's disease , dementia , alzheimer's disease neuroimaging initiative , disease , pathology , endocrinology , psychiatry
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.