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

Abstract

Alzheimer'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 patients' 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 were 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 CD171 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-5p, and mir223-3p correlated with disease severity. Neural damage, specific miRNA downregulation, and inflammatory cytokine upregulation, found in patients' EVs, might be used as a biomarker reflecting AD severity.

MiR‐223‐3p and miR‐22‐3p inhibit monosodium urate‐induced gouty inflammation by targeting NLRP3

“…Recent studies have shown that miR‐223‐3p and miR‐22‐3p are related to the inflammatory factors in some diseases. MiR‐223‐3p can serve as a biomarker of disease severity in pelvic inflammatory disease and Alzheimer's disease 12,13 . MiR‐223‐3p plays a vital role in inflammatory processes and negatively regulates neutrophil chemotaxis and the expression of C‐X‐C ligand 2, C‐C ligand 3, and IL‐6 proteins 14,15 .…”

Multifaceted Regulation of MicroRNA Biogenesis: Essential Roles and Functional Integration in Neuronal and Glial Development

“…A recent report revealed that miR-23a-3p, miR-126-3p, and miR-151a-3p are significantly reduced in brain-derived plasma EVs from AD patients compared to controls [198]. In a separate cohort, the levels of miR-126-3p, miR-142-3p, miR-146a-5p, and miR-223-3p in brain-derived EVs were reported to correlate with disease severity of AD [199]. Besides neuronal EVs, astrocyte-secreted EVs also contain unique miRNAs.…”

Extracellular Vesicles Reflect the Efficacy of Wheatgrass Juice Supplement in Colon Cancer Patients During Adjuvant Chemotherapy

“…This study does not intend to separate between the large and small vesicles populations (MVs and exosomes). EVs were isolated as described previously (15,16). Briefly, 15 ml of peripheral venous blood were drawn from study participants into sodium citrate (3.2%) tubes; platelet-poor plasma (PPP) was obtained after two centrifugations (15 min, 1500 g) within an hour of collection and frozen at −80 • C. EVs size, concentration, and membrane antigens levels were validated on PPP samples.…”