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

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.