Detection of neuron-derived pathological α-synuclein in blood.
In: Brain: A Journal of Neurology, Jg. 145 (2022-09-01), Heft 9, S. 3058-3071
academicJournal
Zugriff:
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 α-synuclein. Pathological α-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 α-synuclein seeding assay these soluble conformers could be amplified and seeding of pathological protein folding was demonstrated. Amplified α-synuclein conformers exhibited β-sheet-rich structures and a fibrillary appearance. Our study demonstrates that the detection of pathological α-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 α-synuclein within blood exosomes sheds a new light of pathological disease mechanisms in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]
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Titel: |
Detection of neuron-derived pathological α-synuclein in blood.
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Autor/in / Beteiligte Person: | Kluge, Annika ; Bunk, Josina ; Schaeffer, Eva ; Drobny, Alice ; Xiang, Wei ; Knacke, Henrike ; Bub, Simon ; Lückstädt, Wiebke ; Arnold, Philipp ; Lucius, Ralph ; Berg, Daniela ; Zunke, Friederike |
Zeitschrift: | Brain: A Journal of Neurology, Jg. 145 (2022-09-01), Heft 9, S. 3058-3071 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 0006-8950 (print) |
DOI: | 10.1093/brain/awac115 |
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