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Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.

Publication ,  Journal Article
Baloni, P; Funk, CC; Yan, J; Yurkovich, JT; Kueider-Paisley, A; Nho, K; Heinken, A; Jia, W; Mahmoudiandehkordi, S; Louie, G; Saykin, AJ ...
Published in: Cell Rep Med
November 17, 2020

Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline.

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Published In

Cell Rep Med

DOI

EISSN

2666-3791

Publication Date

November 17, 2020

Volume

1

Issue

8

Start / End Page

100138

Location

United States

Related Subject Headings

  • Transcriptome
  • Metabolomics
  • Metabolic Networks and Pathways
  • Lipogenesis
  • Lipid Metabolism
  • Humans
  • Cognitive Dysfunction
  • Cholesterol
  • Brain
  • Bile Acids and Salts
 

Citation

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Baloni, P., Funk, C. C., Yan, J., Yurkovich, J. T., Kueider-Paisley, A., Nho, K., … Price, N. D. (2020). Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease. Cell Rep Med, 1(8), 100138. https://doi.org/10.1016/j.xcrm.2020.100138
Baloni, Priyanka, Cory C. Funk, Jingwen Yan, James T. Yurkovich, Alexandra Kueider-Paisley, Kwangsik Nho, Almut Heinken, et al. “Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.Cell Rep Med 1, no. 8 (November 17, 2020): 100138. https://doi.org/10.1016/j.xcrm.2020.100138.
Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, et al. Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease. Cell Rep Med. 2020 Nov 17;1(8):100138.
Baloni, Priyanka, et al. “Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.Cell Rep Med, vol. 1, no. 8, Nov. 2020, p. 100138. Pubmed, doi:10.1016/j.xcrm.2020.100138.
Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, Heinken A, Jia W, Mahmoudiandehkordi S, Louie G, Saykin AJ, Arnold M, Kastenmüller G, Griffiths WJ, Thiele I, Alzheimer’s Disease Metabolomics Consortium, Kaddurah-Daouk R, Price ND. Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease. Cell Rep Med. 2020 Nov 17;1(8):100138.

Published In

Cell Rep Med

DOI

EISSN

2666-3791

Publication Date

November 17, 2020

Volume

1

Issue

8

Start / End Page

100138

Location

United States

Related Subject Headings

  • Transcriptome
  • Metabolomics
  • Metabolic Networks and Pathways
  • Lipogenesis
  • Lipid Metabolism
  • Humans
  • Cognitive Dysfunction
  • Cholesterol
  • Brain
  • Bile Acids and Salts