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Detection of neuron-derived pathological α-synuclein in blood
Annika Kluge 1, Josina Bunk 2, Eva Schaeffer 1, Alice Drobny 3, Wei Xiang 3, Henrike Knacke 1, Simon Bub 3, Wiebke Lückstädt 4, Philipp Arnold 5, Ralph Lucius 4, Daniela Berg 1, Friederike Zunke 3
...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...