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

Hengxing Zheng, Zhenhua Xie, Xuran Zhang, Jian Mao, Mengyuan Wang, Sijia Wei, Yiwen Fu, Hong Zheng, Ying He, Hui Chen, Yan Xu

Neuroscience 2021 Aug 10

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α-Synuclein (α-syn), especially its abnormal oligomeric and phosphorylated form, plays a critical role in the pathogenesis of Parkinson's disease (PD). Plasma exosomal α-syn species have been shown to be a promising PD biomarker. However, whether different α-syn species in plasma exosomes (the oligomeric α-syn and the Ser129 phosphorylated α-syn (p-α-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 α-syn and p-α-syn in the plasma exosomes between PD patients and healthy controls were further analyzed. The results suggested that α-syn and p-α-syn in the plasma exosomes of PD patients showed poor solubility after protease K (PK) treatment. Aggregated α-syn and p-α-syn existed both inside and on the membrane surface of plasma exosomes. The Receiver operating characteristic (ROC) performance of α-syn oligomer/total α-syn in exosomes was moderately helpful in PD diagnosis (AUC = 0.71, sensitivity = 60.5%, specificity = 59.4%), and the ratio of p-α-syn oligomer/total p-α-syn showed similar result (AUC = 0.69, sensitivity = 60.0%, specificity = 59.5%). This study indicates that the oligomeric α-syn/total α-syn and oligomeric p-α-syn/total p-α-syn ratio in plasma exosomes may be applied to assist the PD diagnosis, which needs further research. Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Citation

Hengxing Zheng, Zhenhua Xie, Xuran Zhang, Jian Mao, Mengyuan Wang, Sijia Wei, Yiwen Fu, Hong Zheng, Ying He, Hui Chen, Yan Xu. Investigation of α-Synuclein Species in Plasma Exosomes and the Oligomeric and Phosphorylated α-Synuclein as Potential Peripheral Biomarker of Parkinson's Disease. Neuroscience. 2021 Aug 10;469:79-90