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Metabolic Alterations in the Outer Membrane Vesicles of Patients with Alzheimer’s Disease: An LC-MS/MS-based Metabolomics Analysis

[ Vol. 16 , Issue. 13 ]

Author(s):

Shou-Chao Wei, Wei Wei, Wan-Juan Peng, Zhou Liu*, Zhi-You Cai* and Bin Zhao*   Pages 1183 - 1195 ( 13 )

Abstract:


Objective: To characterize the specific metabolomics profiles in the outer membrane vesicles (OMVs) of patients with Alzheimer’s Disease (AD) and to explore potential metabolic biomarkers and their diagnostic roles.

Methods: Nine AD patients and age- and sex-matched healthy controls were enrolled, and feces were collected. OMVs were extracted, purified, and then analyzed using liquid chromatography-tandem mass chromatography (LC-MS/MS) method coupled with a series of multivariate statistical analyses.

Results: Remarkable differences were found between the OMVs from AD patients and those from healthy controls. A number of differential metabolites and several top-altered metabolic pathways were identified. The levels of aspartate, L-aspartate, imidazole-4-acetate and L-glutamate were confirmed to be highly upregulated in AD-OMVs. Other differential metabolites, such as arachidic acid, prostaglandin G2, and leukotriene B4, were also identified. Furthermore, the differential metabolites possessed higher areas under the ROC curve (AUCs).

Conclusion: Metabolic activity is significantly altered in the OMVs from AD patients. This data might be helpful for identifying novel biomarkers and their diagnostic roles in AD.

Furthermore, OMVs metabolomics analysis combined with GWAS could enrich our understanding of the genetic spectrum of AD and lead to early predictions and diagnosis and clinical applications of better AD treatments.

Keywords:

Alzheimer’s disease, outer membrane vesicles, metabolomics, dementia, LC-MS/MS, genome-wide association studies.

Affiliation:

Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Health Department, Gaomi People's Hospital, Weifang Medical University, Gaomi, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Chongqing Key Laboratory of Neurodegenerative Diseases Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang



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