Objective: This study aimed to identify subsets of plasma EV-associated miRNAs with diagnostic potential for PD and iRBD, the prodromal stage of PD.

Background: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and predominately affects dopamine-producing neurons. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is recognized as the prodromal stage of synucleinopathies, including PD. A minimally invasive test for the early detection and monitoring of iRBD and PD is a highly unmet need for developing drugs and planning patient care. Extracellular vesicles (EVs)  are found in a wide variety of biofluids, including plasma. Numerous examples of EV-mediated functional transfer of microRNAs (miRNAs) have been demonstrated in both in vitro and in vivo models for a variety of diseases and physiological states with a broad range of downstream effects, suggesting that miRNAs are viable candidates as biomarkers for neurodegenerative diseases, especially PD and iRBD.

Method: Next-generation sequencing (NGS) of EV-derived small RNAs was performed in 60 normal controls, 56 iRBD patients and 53 PD patients. Full-scale miRNA profiles of plasma EVs were evaluated by machine-learning methods. Statistical and bioinformatics analyses were carried out to identify the optimal signature of plasma EV-miRNAs as diagnostic biomarkers for detecting iRBD and PD.

Results: Three classification scenarios were investigated by splitting the samples into training and validation sets. First, a three-miRNA signature was found to distinguish iRBD patients and normal controls with a sensitivity of 92.1% (95% CI: 90.9%-93.4%), a specificity of 86.3% (95% CI: 84.7%-87.8%) and an accuracy of 89.2% (88.4%-90%). Second, a fifteen-miRNA signature was found to distinguish PD patients and normal controls with a sensitivity of 86.5% (95% CI, 84.6%-88.5%), a specificity of 77.8% (95% CI, 76%-79.6%) and an accuracy of 82.1% (95% CI, 80.8%-83.3%). Third, an eight-miRNA signature was found to distinguish PD patients and iRBD patients with a sensitivity of 79.6% (95% CI, 78%-81.2%), a specificity of 86.6%(95% CI, 84.9%-88.4%) and an accuracy of 82.8% (95% CI, 81.9%-83.7%).

Conclusion: The study provides a panel of plasma EV-miRNAs that may be used as minimally invasive biomarkers for the detection of PD and its prodromal stage iRBD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/next-generation-sequencing-of-plasma-associated-extracellular-vesicle-mirnas-as-potential-biomarkers-for-parkinsons-disease-and-its-prodromal-stage/