Erythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson’s disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma. Using newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) α-Syn, separated into membrane and cytosolic components, were measured in 225 PD patients and 133 healthy controls and analyzed with extensive clinical measures. The total and aggregated α-Syn levels were significantly higher in the membrane fraction of PD patients compared to healthy controls, but without alterations in the cytosolic component. The pS129 level was remarkably higher in PD subjects than in controls in the cytosolic fraction, and to a lesser extent, higher in the membrane fraction. Combining age, erythrocytic membrane aggregated α-Syn, and cytosolic pS129 levels, a model generated by using logistic regression analysis was able to discriminate patients with PD from neurologically normal controls, with a sensitivity and a specificity of 72 and 68%, respectively. These results suggest that total, aggregated and phosphorylated α-Syn levels are altered in PD erythrocytes and peripheral erythrocytic α-Syn is a potential PD biomarker that needs further validation.

中文翻译：

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红细胞α-突触核蛋白作为帕金森病的潜在生物标志物

红细胞是外周α-突触核蛋白 (α-Syn) 的主要来源。目前调查的目的是评估红细胞总数、寡聚/聚集和磷酸化 α-Syn 物种作为帕金森病 (PD) 的生物标志物。收集 PD 和健康对照血液样本以及广泛的临床病史，以确定来自红细胞（血液 α-Syn 的主要来源）的总的、磷酸化的或聚集的 α-Syn 是否比游离 α 更有希望和一致的 PD 生物标志物-血清或血浆中的Syn物种。使用新开发的电化学发光测定法，在 225 名 PD 患者和 133 名健康对照中测量了红细胞总浓度、聚集和磷酸化 Ser129 (pS129) α-Syn，分为膜和细胞溶质成分，并通过广泛的临床措施进行了分析。与健康对照相比，PD 患者的膜部分中的总和聚合的 α-Syn 水平显着更高，但细胞溶质成分没有改变。PD 受试者的 pS129 水平在细胞溶质部分显着高于对照，在较小程度上，在膜部分更高。结合年龄、红细胞膜聚集的 α-Syn 和细胞溶质 pS129 水平，使用逻辑回归分析生成的模型能够区分 PD 患者和神经正常对照，灵敏度和特异性分别为 72% 和 68%。这些结果表明，PD 红细胞中总的、聚集的和磷酸化的 α-Syn 水平发生了改变，外周红细胞 α-Syn 是一种潜在的 PD 生物标志物，需要进一步验证。