α-Synuclein in Plasma-Derived Extracellular Vesicles Is a Potential Biomarker of Parkinson's Disease

Background Extracellular vesicles are small vesicles that are released from many cells, including neurons. alpha-Synuclein has recently been described in extracellular vesicles derived from the central nervous system and may contribute to the spreading of disease pathology in alpha-synuclein-related neurodegeneration. Objectives We aimed to examine the potential diagnostic value of alpha-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD). Methods Preanalytical variables were studied to establish an optimized assay for preparation of plasma extracellular vesicles and detection of extracellular vesicle-derived alpha-synuclein. Plasma samples were obtained from 2 independent cohorts. The Tubingen cohort contained 96 patients with PD, 50 patients with dementia with Lewy bodies, 50 patients with progressive supranuclear palsy (PSP), and 42 healthy controls; the Kassel cohort included 47 patients with PD, 43 patients with dementia with Lewy bodies, and 36 controls with secondary parkinsonian syndromes. Extracellular vesicles were prepared from total plasma by size exclusion chromatography and quantified by nanoparticle tracking analysis, alpha-synuclein content was measured by an electrochemiluminescence assay. Results alpha-Synuclein concentration in plasma extracellular vesicles provided the best discrimination between PD, dementia with Lewy bodies, PSP, and healthy controls, with an area under the curve of 0.804 (PD vs dementia with Lewy bodies), 0.815 (PD vs. PSP), and 0.769 (PD vs healthy controls) in the Tubingen cohort. Results were validated in the Kassel cohort. Conclusions The concentration of alpha-synuclein in plasma extracellular vesicles may serve as a potential diagnostic biomarker for PD. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Automated summary

This study aimed to examine the diagnostic value of alpha-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD). Results showed that alpha-synuclein concentration in plasma extracellular vesicles could provide good discrimination between different neurodegenerative diseases, suggesting its potential as a diagnostic biomarker for PD. The study highlights the importance of extracellular vesicle-derived alpha-synuclein in disease pathology and diagnosis.