Detection of neuron-derived pathological alpha-synuclein in blood

Kluge A, Bunk J, Schaeffer E, Drobny A, Xiang W, Knacke H, Bub S, Lueckstaedt W, Arnold P, Lucius R, Berg D, Zunke F (2022)

Publication Type: Journal article

Publication year: 2022


DOI: 10.1093/brain/awac115


To date, no reliable clinically applicable biomarker has been established for Parkinson's disease. Our results indicate that a long anticipated blood test for Parkinson's disease may be realized. Following the isolation of neuron-derived extracellular vesicles of Parkinson's disease patients and non-Parkinson's disease individuals, immunoblot analyses were performed to detect extracellular vesicle-derived alpha-synuclein. Pathological alpha-synuclein forms derived from neuronal extracellular vesicles could be detected under native conditions and were significantly increased in all individuals with Parkinson's disease and clearly distinguished disease from the non-disease state. By performing an alpha-synuclein seeding assay these soluble conformers could be amplified and seeding of pathological protein folding was demonstrated. Amplified alpha-synuclein conformers exhibited beta-sheet-rich structures and a fibrillary appearance. Our study demonstrates that the detection of pathological alpha-synuclein conformers from neuron-derived extracellular vesicles from blood plasma samples has the potential to evolve into a blood-biomarker of Parkinson's disease that is still lacking so far. Moreover, the distribution of seeding-competent alpha-synuclein within blood exosomes sheds a new light of pathological disease mechanisms in neurodegenerative disorders.

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Kluge, A., Bunk, J., Schaeffer, E., Drobny, A., Xiang, W., Knacke, H.,... Zunke, F. (2022). Detection of neuron-derived pathological alpha-synuclein in blood. Brain.


Kluge, Annika, et al. "Detection of neuron-derived pathological alpha-synuclein in blood." Brain (2022).

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