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

Journal

Brain Oxford University Press

DOI: 10.1093/brain/awac115

Abstract

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.

Authors with CRIS profile

Alice Drobny Department of Molecular Neurology Wei Xiang Department of Molecular Neurology Simon Bub Department of Molecular Neurology Philipp Arnold Lehrstuhl für Funktionelle und Klinische Anatomie Friederike Zunke Juniorprofessur für Translationale Neurowissenschaften

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

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. https://dx.doi.org/10.1093/brain/awac115

MLA:

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

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