Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease

Xaiobei Pan, Christopher T Elliott, Bernadette McGuinness, Peter Passmore, Patrick Kehoe, Christian Holscher, Paula L McClean, Stewart F Graham, Brian D Green

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer’s disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10). In addition, we also profiled brain/plasma samples from APP/PS1 and WT mice (aged 6 and 12 months). In human plasma, we detected significantly lower cholic acid (CA, p = 0.03) in AD patients than age-matched control subjects. In APP/PS1 mouse plasma we detected higher CA (p = 0.05, 6 months) and lower hyodeoxycholic acid (p = 0.04, 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) taurocholic acid (TCA) were significantly lower (p = 0.01) than age-matched control subjects. In APP/PS1 mice we detected higher brain lithocholic acid (p = 0.05) and lower tauromuricholic acid (TMCA; p = 0.05, 6 months). TMCA was also decreased (p = 0.002) in 12-month-old APP/PS1 mice along with 5 other acids: CA (p = 0.02), β-muricholic acid (p = 0.02), Ω-muricholic acid (p = 0.05), TCA (p = 0.04), and tauroursodeoxycholic acid (p = 0.02). The levels of bile acids are clearly disturbed during the development of AD pathology and, since some bile acids are being proposed as potential AD therapeutics, we demonstrate a method that can be used to support work to advance bile acid therapeutics.
LanguageEnglish
JournalMetabolites
Volume7
Issue number2
DOIs
Publication statusAccepted/In press - 14 Jun 2017

Fingerprint

Metabolomics
Bile Acids and Salts
Alzheimer Disease
Brain
Taurocholic Acid
Lithocholic Acid
Pathology
Cholic Acid
Anti-Inflammatory Agents
Therapeutics
Acids

Keywords

  • bile acids
  • metabolomics
  • Alzheimer’s disease
  • metabolites

Cite this

Pan, X., Elliott, C. T., McGuinness, B., Passmore, P., Kehoe, P., Holscher, C., ... Green, B. D. (Accepted/In press). Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease. Metabolites, 7(2). https://doi.org/10.3390/metabo7020028
Pan, Xaiobei ; Elliott, Christopher T ; McGuinness, Bernadette ; Passmore, Peter ; Kehoe, Patrick ; Holscher, Christian ; McClean, Paula L ; Graham, Stewart F ; Green, Brian D. / Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease. In: Metabolites. 2017 ; Vol. 7, No. 2.
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Pan, X, Elliott, CT, McGuinness, B, Passmore, P, Kehoe, P, Holscher, C, McClean, PL, Graham, SF & Green, BD 2017, 'Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease', Metabolites, vol. 7, no. 2. https://doi.org/10.3390/metabo7020028

Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease. / Pan, Xaiobei; Elliott, Christopher T; McGuinness, Bernadette; Passmore, Peter; Kehoe, Patrick; Holscher, Christian; McClean, Paula L; Graham, Stewart F; Green, Brian D.

In: Metabolites, Vol. 7, No. 2, 14.06.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer’s Disease

AU - Pan, Xaiobei

AU - Elliott, Christopher T

AU - McGuinness, Bernadette

AU - Passmore, Peter

AU - Kehoe, Patrick

AU - Holscher, Christian

AU - McClean, Paula L

AU - Graham, Stewart F

AU - Green, Brian D

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N2 - Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer’s disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10). In addition, we also profiled brain/plasma samples from APP/PS1 and WT mice (aged 6 and 12 months). In human plasma, we detected significantly lower cholic acid (CA, p = 0.03) in AD patients than age-matched control subjects. In APP/PS1 mouse plasma we detected higher CA (p = 0.05, 6 months) and lower hyodeoxycholic acid (p = 0.04, 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) taurocholic acid (TCA) were significantly lower (p = 0.01) than age-matched control subjects. In APP/PS1 mice we detected higher brain lithocholic acid (p = 0.05) and lower tauromuricholic acid (TMCA; p = 0.05, 6 months). TMCA was also decreased (p = 0.002) in 12-month-old APP/PS1 mice along with 5 other acids: CA (p = 0.02), β-muricholic acid (p = 0.02), Ω-muricholic acid (p = 0.05), TCA (p = 0.04), and tauroursodeoxycholic acid (p = 0.02). The levels of bile acids are clearly disturbed during the development of AD pathology and, since some bile acids are being proposed as potential AD therapeutics, we demonstrate a method that can be used to support work to advance bile acid therapeutics.

AB - Certain endogenous bile acids have been proposed as potential therapies for ameliorating Alzheimer’s disease (AD) but their role, if any, in the pathophysiology of this disease is not currently known. Given recent evidence of bile acids having protective and anti-inflammatory effects on the brain, it is important to establish how AD affects levels of endogenous bile acids. Using LC-MS/MS, this study profiled 22 bile acids in brain extracts and blood plasma from AD patients (n = 10) and age-matched control subjects (n = 10). In addition, we also profiled brain/plasma samples from APP/PS1 and WT mice (aged 6 and 12 months). In human plasma, we detected significantly lower cholic acid (CA, p = 0.03) in AD patients than age-matched control subjects. In APP/PS1 mouse plasma we detected higher CA (p = 0.05, 6 months) and lower hyodeoxycholic acid (p = 0.04, 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) taurocholic acid (TCA) were significantly lower (p = 0.01) than age-matched control subjects. In APP/PS1 mice we detected higher brain lithocholic acid (p = 0.05) and lower tauromuricholic acid (TMCA; p = 0.05, 6 months). TMCA was also decreased (p = 0.002) in 12-month-old APP/PS1 mice along with 5 other acids: CA (p = 0.02), β-muricholic acid (p = 0.02), Ω-muricholic acid (p = 0.05), TCA (p = 0.04), and tauroursodeoxycholic acid (p = 0.02). The levels of bile acids are clearly disturbed during the development of AD pathology and, since some bile acids are being proposed as potential AD therapeutics, we demonstrate a method that can be used to support work to advance bile acid therapeutics.

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KW - metabolomics

KW - Alzheimer’s disease

KW - metabolites

U2 - 10.3390/metabo7020028

DO - 10.3390/metabo7020028

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VL - 7

JO - Metabolites

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