Objective: To identify differentially expressed small extracellular vesicles (sEV) derived miRNAs in Parkinson’s disease using small RNA-sequencing and to evaluate their potential as biomarker targets.

Background: Parkinson’s disease is an increasingly common neurodegenerative condition, which not only causes dysfunction of movement but also a broad range of nonmotor symptoms. There is no objective molecular or biochemical diagnostic test for PD as of yet. sEV are known to transverse the blood brain barrier hence, miRNA enriched in sEV not only reflects the molecular state of the secreting cell, but also can be studied for its immense potential as a diagnostic tool.

Method: We recruited 48 subjects-16 PD (Age: 55.6 ± 14.2 years, Male: 81.3%), 16 aged-matched (Age: 55.2 ± 12.7, Male: 81.3%) and 16 young controls (Age: 25.9 ± 2.5 years, Male:87.5%). The sEV were isolated, characterized and validated following Minimal information for studies of extracellular vesicles (MISEV) guidelines. Small RNA isolation, library preparation, small RNA sequencing followed by differential expression analysis and target prediction were performed. Quantitative PCR (qPCR) was done for validation of the selected miRNAs in both the plasma and plasma-derived sEV fractions.

Results: We identified 263 miRNAs specific to the PD group, out of which 14.89% were up-regulated and 16.54% were downregulated. The expression of miR-23b-3p was upregulated in plasma (p=0.002) and downregulated in plasma-derived sEVs (p=0.028). The ROC analysis of miR-23b-3p showed plasma AUC values (AUC= 0.809, p=0.003) was higher compared to plasma-derived EVs (AUC= 0.727, p= 0.048) between PD and age-matched controls. However, the same trend was not observed when we compared the PD group with young healthy control.

Conclusion: The miR-23b-3p expression level were opposite in plasma and plasma-derived miRNAs, difference was also observed between the young and age-matched healthy controls in the plasma-derived fraction only. 3’UTR of SNCA gene which encodes Alpha-synuclein protein is the putative target for miR-23b-3p. The observed disparity in our study implies a subtle regulation of miR-23b-3p and necessitates further studies to understand the role of miR-23b-3p not only in terms of disease pathophysiology but also in healthy physiological system.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-small-extracellular-vesicles-derived-mirna-as-biomarkers-for-parkinsons-disease-comparison-with-plasma-mirna/