Detection of neuron-derived pathological α-synuclein in blood

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 p...

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Vydané v:Brain (London, England : 1878) Ročník 145; číslo 9; s. 3058
Hlavní autori: Kluge, Annika, Bunk, Josina, Schaeffer, Eva, Drobny, Alice, Xiang, Wei, Knacke, Henrike, Bub, Simon, Lückstädt, Wiebke, Arnold, Philipp, Lucius, Ralph, Berg, Daniela, Zunke, Friederike
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England 14.09.2022
Predmet:
alpha-Synuclein - metabolism
Biomarkers - metabolism
Exosomes - metabolism
Humans
Neurons - metabolism
Parkinson Disease - metabolism
neuron-derived extracellular vesicles
seeding assay
biomarker
Parkinson’s disease
α-synuclein
ISSN:1460-2156, 1460-2156
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1460-2156
1460-2156
DOI:10.1093/brain/awac115