Profile of Pathogenic Proteins and MicroRNAs in Plasma-derived Extracellular Vesicles in Alzheimer's Disease: A Pilot Study

Abstract

Protein and miRNA enrichment within extracellular vesicles (EVs) isolated from patients with Alzheimer's disease (AD) has been shown to have putative diagnostic value. However, whether a combination of both will be more advantageous is unknown. EVs were enriched from serum samples obtained from patients with sporadic AD (n = 13), mild cognitive impairment (MCI) (n = 10), vascular dementia (VaD) (n = 10), and healthy controls (HC) (n = 10). Expression of protein levels of beta-amyloid peptide (Aβ1-42), total tau, P-T181-tau, and P-S396-tau and 18 microRNAs (miRNAs) in the EVs was performed by ELISA and qRT-PCR, respectively. Results were validated in an independent cohort of 18 subjects each by qRT-PCR assays. EV protein expression of Aβ1-42, total-tau, P-T181-tau and P-S396-tau, were significantly different among AD, MCI and VaD. Hsa-miR-1306-5p, hsa-miR-342-3p, and hsa-15b-3p were all significantly downregulated in patients with AD compared to HC (P < 0.05), only hsa-miR-1306-5p expression was differentially expressed between AD, MCI, and VaD samples. Similarly, whereas all 14 miRNAs were significantly upregulated in patients with AD compared to HC, only hsa-miR-93-5p, hsa-miR-424-5p, and hsa-miR-3065-5p were differentially expressed when AD samples were compared to MCI and VaD samples. Even though the sample size was small, the results of the current pilot study indicates that hsa-miR-1306-5p, hsa-miR-93-5p, hsa-miR-424-5p, and hsa-miR-3065-5p, and expression of P-S396-tau in EVs might provide a combinatorial protein and miRNA signature to differentiate between HC, patients with MCI or VaD from patient with sporadic AD.

Keywords: Alzheimer’s disease; dementia; extracellular vesicle; microRNA; pathogenic proteins.