Altered bile acid profile in mild cognitive impairment and Alzheimer's disease

Relationship to neuroimaging and CSF biomarkers

Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)232-244
Number of pages13
JournalAlzheimer's and Dementia
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Bile Acids and Salts
Neuroimaging
Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Amyloid
Atrophy
Glucose
Metabolomics
Cognitive Dysfunction
Microbiota
Serum
Causality
Quality Control
Cholesterol
Magnetic Resonance Imaging
Brain

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Bile acid
  • Brain glucose metabolism
  • CSF biomarkers
  • Gut-liver-brain axis
  • Metabolomics
  • MRI
  • PET

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Altered bile acid profile in mild cognitive impairment and Alzheimer's disease : Relationship to neuroimaging and CSF biomarkers. / Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium.

In: Alzheimer's and Dementia, Vol. 15, No. 2, 01.02.2019, p. 232-244.

Research output: Contribution to journalArticle

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 and Dementia, vol. 15, no. 2, pp. 232-244. https://doi.org/10.1016/j.jalz.2018.08.012
Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium. / Altered bile acid profile in mild cognitive impairment and Alzheimer's disease : Relationship to neuroimaging and CSF biomarkers. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 2. pp. 232-244.
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abstract = "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.",
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T1 - Altered bile acid profile in mild cognitive impairment and Alzheimer's disease

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AU - Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium

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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

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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.

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KW - PET

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