Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.

中文翻译：

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帕金森病患者血液中的聚集抗性 α-突触核蛋白四聚体减少。


帕金森病 （PD） 等突触核蛋白病的定义是 α-突触核蛋白在神经元、神经胶质细胞和其他组织中的积累和聚集。我们之前已经表明，α-突触核蛋白四聚体的不稳定与 SNCA 突变引起的家族性 PD 有关，并证明了散发性 PD 患者α-突触核蛋白多聚体的脑区特异性改变遵循经典的 Braak 扩散理论。在这项研究中，我们评估了具有 G51D 突变的家族性 PD 和散发性 PD 患者血液中细胞溶质 α-突触核蛋白的无序和高阶多聚体形式的相对水平。我们对人 EDTA 全血使用了适应性强的体外交联方案。与对照组相比，家族性 PD 和散发性 PD 患者血液中高阶 α-突触核蛋白四聚体的相对水平降低。有趣的是，在无症状的 G51D 携带者中，α-突触核蛋白四聚体的相对量已经降低，这支持 α-突触核蛋白多聚体不稳定先于临床 PD 发展的假设。因此，我们的数据表明，测量血液中的 α-突触核蛋白四聚体可能具有作为早期检测和定量跟踪 PD 进展的简单生物标志物测定的潜力。