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

Abstract EN

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.