Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China.
Department of Pathology, Peking University School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Department of Pathology, Peking University Third Hospital, Peking University, Beijing, 100191, China; Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers, Beijing, 100191, China.
Parkinsonism Relat Disord. 2019 Mar;60:105-110. doi: 10.1016/j.parkreldis.2018.09.012. Epub 2018 Sep 11.
Multiple system atrophy(MSA) is a neurodegenerative disease characterized by intracellular α-synuclein deposits. There is an unmet need for blood-based biomarkers to diagnose MSA. Our previous studies have reported elevated α-synuclein levels in erythrocytes of MSA patients. However, α-synuclein protein in the membrane and cytoplasm of erythrocytes in MSA have not been investigated.
The membrane and cytoplasm were extracted from erythrocytes in 77 patients with MSA and 133 healthy controls. Levels of total and oligomeric α-synuclein were detected using Electrochemiluminescence assays. The correlations between α-synuclein levels and clinical characteristics were explored in MSA group. The diagnostic value of erythrocyte α-synuclein for MSA was determined by Receiver operator characteristic curve.
α-synuclein levels in the erythrocyte membrane were significantly elevated in MSA patients compared with the healthy controls (total α-synuclein, p = 0.003; oligomeric α-synuclein/total α-synuclein, p = 0.033; oligomeric α-synuclein/protein, p < 0.001). The combination of total and oligomeric α-synuclein levels in erythrocyte membrane could efficiently distinguish MSA from healthy controls (sensitivity of 79.2%; specificity of 69.2%; area under the curve: 0.771). In contrast, no significant difference was found in erythrocyte cytoplasm α-synuclein levels. In the subgroup of 48 patients with probable MSA, there was a weakly negative correlation between oligomeric α-synuclein/protein in erythrocyte membrane and disease duration (r = -0.336; p = 0.009).
Our pilot study suggests that the membrane fraction of α-synuclein levels in erythrocyte were elevated in patients with MSA, and these levels may be decreased with the development of disease.
多系统萎缩（MSA）是一种以细胞内α-突触核蛋白沉积为特征的神经退行性疾病。目前，人们迫切需要血液生物标志物来诊断 MSA。我们之前的研究报告称，MSA 患者的红细胞中α-突触核蛋白水平升高。然而，MSA 患者红细胞的膜和细胞质中的α-突触核蛋白尚未得到研究。
从 77 例 MSA 患者和 133 例健康对照者的红细胞中提取膜和细胞质。使用电化学发光测定法检测总α-突触核蛋白和寡聚体α-突触核蛋白的水平。在 MSA 组中探讨α-突触核蛋白水平与临床特征的相关性。通过接收者操作特征曲线确定红细胞α-突触核蛋白对 MSA 的诊断价值。
与健康对照组相比，MSA 患者红细胞膜中的α-突触核蛋白水平显著升高（总α-突触核蛋白，p=0.003；寡聚体α-突触核蛋白/总α-突触核蛋白，p=0.033；寡聚体α-突触核蛋白/蛋白，p<0.001）。红细胞膜中总α-突触核蛋白和寡聚体α-突触核蛋白的组合能够有效地将 MSA 与健康对照组区分开来（敏感性为 79.2%；特异性为 69.2%；曲线下面积：0.771）。相比之下，红细胞细胞质中的α-突触核蛋白水平无显著差异。在 48 例可能的 MSA 患者亚组中，红细胞膜中寡聚体α-突触核蛋白/蛋白与疾病持续时间之间存在弱负相关（r=-0.336；p=0.009）。
我们的初步研究表明，MSA 患者红细胞的膜部分α-突触核蛋白水平升高，并且这些水平可能随着疾病的发展而降低。
