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.

中文翻译：

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检测血液中神经元来源的病理性α-突触核蛋白。

迄今为止，还没有针对帕金森病建立可靠的临床适用生物标志物。我们的结果表明，期待已久的帕金森病血液检测可能会实现。在分离帕金森病患者和非帕金森病个体的神经元来源的细胞外囊泡后，进行免疫印迹分析以检测细胞外囊泡来源的 α-突触核蛋白。源自神经元细胞外囊泡的病理性 α-突触核蛋白形式可以在自然条件下检测到，并且在所有帕金森病患者中显着增加，并且可以清楚地区分疾病与非疾病状态。通过进行 α-突触核蛋白接种试验，可以扩增这些可溶性构象异构体，并证明病理性蛋白质折叠的接种。扩增的 α-突触核蛋白构象异构体表现出富含 β-折叠的结构和纤维状外观。我们的研究表明，从血浆样本中检测神经元衍生的细胞外囊泡中的病理性 α-突触核蛋白构象异构体有可能演变成帕金森氏病的血液生物标志物，而目前仍缺乏这一点。此外，具有播种能力的 α-突触核蛋白在血液外泌体中的分布为神经退行性疾病的病理疾病机制提供了新的思路。至今仍欠缺的疾病。此外，具有播种能力的 α-突触核蛋白在血液外泌体中的分布为神经退行性疾病的病理疾病机制提供了新的思路。至今仍欠缺的疾病。此外，具有播种能力的 α-突触核蛋白在血液外泌体中的分布为神经退行性疾病的病理疾病机制提供了新的思路。