Extracellular Vesicles of Alzheimer ’s Disease Patients as a Biomarker for Disease Progression

AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patien ts’ EVs on disease progression. Blood samples were collected after obtaining signed informed consent (No. 0462-14-RMB) from 42 AD patients at three stages of disease severity and from 19 healthy controls (HC). EV size and concentration were studied by nanotracking analysis. EV membrane antigens we re defined by flow cytometry and Western blot; EV protein contents were screened by protein array; the miRNA content was screened by nanostring technology and validated by RT-PCR. HC and AD patients’ EVs consisted of a mixture of small (<  100 nm) and larger vesicles. The myelin oligodendrocyte glycoprotein (MOG) expression on EVs correlated with disease severity. EVs of patients with moderate and severe AD had significantly higher levels of MOG, compared with mild AD patients. Levels of EVs expressing the axonal glycoprotein CD17 1 were significantly higher in severe AD patients than in HC. Increase in endothelial EVs was observed in AD patients. An above twofold increase was found in the content of inflammatory cytokines and>  50% decrease in growth factors in AD patients’ EVs compared with HC-EVs. Levels of let-7g-5p, miR126-3p, miR142-3p, miR-146a-5...
Source: Molecular Neurobiology - Category: Neurology Source Type: research