To date, no reliable clinically applicable biomarker has been established for Parkinson’s disease. New 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, researchers from the University Hospital Kiel performed immunoblot analyses 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. This 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.
A blood test for Parkinson’s disease
Kluge A, Bunk J, Schaeffer E, Drobny A, Xiang W, Knacke H, Bub S, Lückstädt W, Arnold P, Lucius R, Berg D, Zunke F. (2022) Detection of neuron-derived pathological α-synuclein in blood. Brain [Epub ahead of print]. [abstract]