German Center for Neurodegenerative Diseases, DZNE, Bonn, Germany.
Department of Neurogenetics, Electron Microscopy Core Unit, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Mov Disord. 2021 Nov;36(11):2508-2518. doi: 10.1002/mds.28639. Epub 2021 May 18.
Extracellular vesicles are small vesicles that are released from many cells, including neurons. α-Synuclein has recently been described in extracellular vesicles derived from the central nervous system and may contribute to the spreading of disease pathology in α-synuclein-related neurodegeneration.
We aimed to examine the potential diagnostic value of α-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD).
Preanalytical variables were studied to establish an optimized assay for preparation of plasma extracellular vesicles and detection of extracellular vesicle-derived α-synuclein. Plasma samples were obtained from 2 independent cohorts. The Tübingen cohort contained 96 patients with PD, 50 patients with dementia with Lewy bodies, 50 patients with progressive supranuclear palsy (PSP), and 42 healthy controls; the Kassel cohort included 47 patients with PD, 43 patients with dementia with Lewy bodies, and 36 controls with secondary parkinsonian syndromes. Extracellular vesicles were prepared from total plasma by size exclusion chromatography and quantified by nanoparticle tracking analysis, α-synuclein content was measured by an electrochemiluminescence assay.
α-Synuclein concentration in plasma extracellular vesicles provided the best discrimination between PD, dementia with Lewy bodies, PSP, and healthy controls, with an area under the curve of 0.804 (PD vs dementia with Lewy bodies), 0.815 (PD vs. PSP), and 0.769 (PD vs healthy controls) in the Tübingen cohort. Results were validated in the Kassel cohort.
The concentration of α-synuclein in plasma extracellular vesicles may serve as a potential diagnostic biomarker for PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
细胞外囊泡是从小鼠细胞中释放的小囊泡，包括神经元。α-突触核蛋白最近在源自中枢神经系统的细胞外囊泡中被描述，并可能有助于与α-突触核蛋白相关的神经退行性疾病中疾病病理学的传播。
我们旨在检查帕金森病（PD）患者血浆细胞外囊泡中α-突触核蛋白的潜在诊断价值。
研究了预分析变量，以建立一种优化的方案来制备血浆细胞外囊泡并检测细胞外囊泡衍生的α-突触核蛋白。从 2 个独立的队列中获得了血浆样本。图宾根队列包含 96 名 PD 患者、50 名路易体痴呆患者、50 名进行性核上性麻痹（PSP）患者和 42 名健康对照者；卡塞尔队列包括 47 名 PD 患者、43 名路易体痴呆患者和 36 名继发性帕金森综合征对照者。通过大小排阻色谱法从总血浆中分离出细胞外囊泡，并通过纳米颗粒跟踪分析进行定量，通过电化学发光法测量α-突触核蛋白含量。
PD、路易体痴呆、PSP 和健康对照组患者血浆细胞外囊泡中α-突触核蛋白的浓度提供了最佳的区分，图宾根队列的曲线下面积分别为 0.804（PD 与路易体痴呆）、0.815（PD 与 PSP）和 0.769（PD 与健康对照组）。结果在卡塞尔队列中得到验证。
血浆细胞外囊泡中α-突触核蛋白的浓度可能是 PD 的潜在诊断生物标志物。© 2021 作者。运动障碍由 Wiley 期刊代表国际帕金森病和运动障碍协会出版。
