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Background: Parkinson’s disease (PD), a severe neurodegenerative disorder, and idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD), a parasomnia recognized as the prodromal stage of synucleinopathies (including PD), both lack reliable, non-invasive biomarker tests for early intervention and management.

Objectives: To investigate whether plasma extracellular vesicle (EV)-associated sncRNAs could discriminate PD and/or iRBD patients from healthy individuals.

Methods: We optimized a cDNA library construction method, EVsmall-seq, for high throughput sequencing of sncRNAs associated with plasma EVs. We pro led EV-sncRNAs from the plasma of 60 normal controls, 56 iRBD patients, and 53 PD patients, and constructed a support vector machine (SVM) classi er to identify the informative miRNA features to distinguish PD and/or iRBD patients from healthy individuals.

Results: First, a sixteen-miRNA signature was found to distinguish PD patients from healthy individuals with 88% sensitivity, 90.43% speci city, and 89.13% accuracy. Second, a three-miRNA signature was found to distinguish iRBD patients from healthy individuals with 96% sensitivity, 86.36% speci city, and 91.49% accuracy. Third, tweenty 20 miRNAs were found consistently increased or decreased in expression from healthy subjects to iRBD to PD patients, which might be linked to PD development through iRBD.

Conclusions: Current study provides a valuable and highly informative dataset of EV-associated sncRNAs from plasma of iRBD and PD patients. We identi ed miRNA signature features that could serve as minimally-invasive, blood-based …