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Parkinson’s Disease
Volume 2016, Article ID 7596482, 14 pages
http://dx.doi.org/10.1155/2016/7596482
Research Article

Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

1Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China
2Department of Human Anatomy, School of Basic Medical Sciences, Beihua University, Jilin, China
3Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China
4Beijing Key Laboratory for Parkinson’s Disease, Beijing, China

Received 23 June 2016; Revised 16 September 2016; Accepted 9 October 2016

Academic Editor: Hélio Teive

Copyright © 2016 Peng Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A pathological hallmark of Parkinson’s disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD.