Investigation of α-Synuclein Species in Plasma Exosomes and the Oligomeric and Phosphorylated α-Synuclein as Potential Peripheral Biomarker of Parkinson's Disease

(a-syn), especially its abnormal oligomeric and phosphorylated form, plays a critical role in the pathogenesis of Parkinson's disease (PD). Plasma exosomal a-syn species have been shown to be a promis-ing PD biomarker. However, whether different a-syn species in plasma exosomes (the oligomeric a-syn and the Ser129 phosphorylated a-syn (p-a-syn)) which represent the PD pathogenesis in the brain could be specific peripheral PD biomarker haven't been well elucidated. In this study, we successfully extracted and identified the human plasma exosomes, and the CNS-derived exosomes were detected. The different aggregation status, localization and degradation characteristics of a-syn and p-a-syn in the plasma exosomes between PD patients and healthy controls were further analyzed. The results suggested that a-syn and p-a-syn in the plasma exosomes of PD patients showed poor solubility after protease K (PK) treatment. Aggregated a-syn and p-a-syn existed both inside and on the membrane surface of plasma exosomes. The Receiver operating characteristic (ROC) perfor-mance of a-syn oligomer/total a-syn in exosomes was moderately helpful in PD diagnosis (AUC = 0.71, sensitivity = 60.5%, specificity = 59.4%), and the ratio of p-a-syn oligomer/total p-a-syn showed similar result (AUC = 0.69, sensitivity = 60.0%, specificity = 59.5%). This study indicates that the oligomeric a-syn/total a -syn and oligomeric p-a-syn/total p-a-syn ratio in plasma exosomes may be applied to assist the PD diagnosis, which needs further research. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study examined the aggregation status, localization, and degradation characteristics of a-syn and p-a-syn in plasma exosomes from PD patients and healthy controls. Results indicated poor solubility of a-syn and p-a-syn after protease K treatment, with aggregates found inside and on the membrane surface of plasma exosomes. The ratios of oligomeric a-syn/total a-syn and oligomeric p-a-syn/total p-a-syn in plasma exosomes showed moderate utility in assisting PD diagnosis.