Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease
Autor: | Baloni, Priyanka, Funk, Cory C, Yan, Jingwen, Yurkovich, James T, Kueider-Paisley, Alexandra, Nho, Kwangsik, Heinken, Almut, Jia, Wei, Mahmoudiandehkordi, Siamak, Louie, Gregory, Saykin, Andrew J, Arnold, Matthias, Kastenmüller, Gabi, Griffiths, William J, Thiele, Ines, Alzheimer’s Disease Metabolomics Consortium, Kaddurah-Daouk, Rima, Price, Nathan D |
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Rok vydání: | 2020 |
Předmět: |
Aging
genome-scale metabolic models Neurodegenerative Alzheimer's Disease Bile Acids and Salts transcriptomics Alzheimer Disease Acquired Cognitive Impairment Genetics Humans Metabolomics 2.1 Biological and endogenous factors Cognitive Dysfunction Aetiology Nutrition bile acids Lipogenesis Liver Disease Alzheimer’s Disease Metabolomics Consortium Neurosciences Brain Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Lipid Metabolism Brain Disorders Cholesterol transcriptional regulatory networks Neurological cholesterol metabolism Dementia Transcriptome Digestive Diseases Metabolic Networks and Pathways |
Zdroj: | Cell reports. Medicine, vol 1, iss 8 |
Popis: | 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. |
Databáze: | OpenAIRE |
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