Objective: The objective of this study is to investigate the role of extracellular vesicles (EVs) in the progression of Parkinson’s disease

Background: Parkinson’s disease (PD) is pathologically characterized by the accumulation of a-synuclein (a-syn) inclusions, known as Lewy bodies/neurites, within both the central nervous system (CNS) and the peripheral nervous system (PNS). Recent research suggests that EVs may contribute to the spreading of Lewy pathology between the PNS and CNS.

Method: We isolated and analyzed serum EVs from patients with PD (n = 142), multiple system atrophy (MSA) (n = 18), progressive supranuclear palsy (PSP) (n = 28), rapid eye movement sleep behavior disorder (n = 31), and controls (n = 105). Additionally, we investigated the effect of EVs in the propagation of a-syn by analyzing mouse brains after injecting a-syn-containing EVs or free a-syn into the mouse brains or mouse tail veins.

Results: A significant reduction in the number of EVs in PD compared to controls (p = 0.002) was observed. In contrast, our ELISA system revealed a substantially increased filamentous α-synuclein within EVs in PD compared to controls (p < 0.0048) and PSP (p = 0.04). Further investigation in mice demonstrated the role of EVs in facilitating the transmission of filamentous α-synuclein between CNS neurons and from peripheral blood to the CNS.

Conclusion: These findings indicate the utility of serum α-synuclein filaments within EVs as diagnostic markers for synucleinopathies. Moreover, they highlight the significant role of EVs in promoting the propagation of filamentous α-synuclein within brains and throughout the entire body.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-extracellular-vesicles-in-the-progression-of-parkinsons-disease/