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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • November 17, 2020

Published In

Volume / Issue

  • 1 / 8

Start / End Page

  • 100138 -

PubMed ID

  • 33294859

Pubmed Central ID

  • PMC7691449

Electronic International Standard Serial Number (EISSN)

  • 2666-3791

Digital Object Identifier (DOI)

  • 10.1016/j.xcrm.2020.100138

Language

  • eng

Conference Location

  • United States