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.

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