Liver Bile Acid Changes in Mouse Models of Alzheimer's Disease.

Autor: Kaur H; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USA., Seeger D; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USA., Golovko S; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USA., Golovko M; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USA., Combs CK; Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Jul 12; Vol. 22 (14). Date of Electronic Publication: 2021 Jul 12.
DOI: 10.3390/ijms22147451
Abstrakt: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and App NL-G-F . Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and App NL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.
Databáze: MEDLINE
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