Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease
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 b...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7451 |
| _version_ | 1797526948076847104 |
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| author | Harpreet Kaur Drew Seeger Svetlana Golovko Mikhail Golovko Colin Kelly Combs |
| author_facet | Harpreet Kaur Drew Seeger Svetlana Golovko Mikhail Golovko Colin Kelly Combs |
| author_sort | Harpreet Kaur |
| collection | DOAJ |
| description | 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 <i>App<sup>NL-G-F</sup></i>. 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 <i>App<sup>NL-G-F</sup></i> 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. |
| first_indexed | 2024-03-10T09:37:32Z |
| format | Article |
| id | doaj.art-b2cbcdf0164d4f76ac9754cef6d23dff |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:37:32Z |
| publishDate | 2021-07-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b2cbcdf0164d4f76ac9754cef6d23dff2023-11-22T03:58:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214745110.3390/ijms22147451Liver Bile Acid Changes in Mouse Models of Alzheimer’s DiseaseHarpreet Kaur0Drew Seeger1Svetlana Golovko2Mikhail Golovko3Colin Kelly Combs4Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USADepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USADepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USADepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USADepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Road, Grand Forks, ND 58202-9037, USAAlzheimer’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 <i>App<sup>NL-G-F</sup></i>. 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 <i>App<sup>NL-G-F</sup></i> 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.https://www.mdpi.com/1422-0067/22/14/7451bile acidsex differenceAlzheimer’s diseasecholesterolcytochrome P450 |
| spellingShingle | Harpreet Kaur Drew Seeger Svetlana Golovko Mikhail Golovko Colin Kelly Combs Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease International Journal of Molecular Sciences bile acid sex difference Alzheimer’s disease cholesterol cytochrome P450 |
| title | Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease |
| title_full | Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease |
| title_fullStr | Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease |
| title_full_unstemmed | Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease |
| title_short | Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease |
| title_sort | liver bile acid changes in mouse models of alzheimer s disease |
| topic | bile acid sex difference Alzheimer’s disease cholesterol cytochrome P450 |
| url | https://www.mdpi.com/1422-0067/22/14/7451 |
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