Li Xu-Ying, Yang Weiwei, Li Xin, Li Xu-Ran, Li Wei, Song Qihan, Sun Linjuan, Lin Feng, Chen Zhigang, Wang Chaodong, Yu Shun
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Department of Neurology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Parkinsons Dis. 2020 Jan 31;2020:8740419. doi: 10.1155/2020/8740419. eCollection 2020.
Diagnosis of multiple system atrophy (MSA) remains a challenge, due to the complexity and overlapping of its symptoms with other Parkinsonian disorders. The critical role of alpha-synuclein (-syn) in the pathogenesis of MSA makes it an ideal biomarker for the diagnosis of MSA. Although -syn alterations in cerebrospinal fluid (CSF) and blood plasma have been extensively assessed for the utility in diagnosing MSA, inconsistent results have been obtained, presumably due to the contamination by hemolysis and other confounding factors. In this study, levels of serine 129-phosphorylated -syn (pS--syn), a major pathologic form of -syn, in red blood cells (RBCs), were measured using ELISA in a Chinese cohort consisting of 107 MSA patients and 220 healthy controls. A significant increase in the levels of pS--syn in RBCs (pS--syn-RBC) was observed in MSA patients than in healthy controls (14.02 ± 4.02 ng/mg versus 11.89 ± 3.57 ng/mg; < 0.0001). Receiver operating characteristic curve (ROC) indicated that pS--syn-RBC discriminated the patients well from the controls with a sensitivity of 80.37% (95% confidence interval (CI): 71.58%-87.42%), a specificity of 88.64% (95% CI: 83.68%-92.51%), and an area under the curve (AUC) of 0.91 (95% CI: 0.87-0.94). The levels of pS--syn-RBC were negatively correlated with RBD-HK scores and differed between MSA-P and MSA-C subtypes (13.27 ± 1.91 versus 12.19 ± 3.04; =0.025). The difference between subtypes was seen at Hoehn and Yahr stages 3 and 4, and the age at onset (AAO) between 60 and 69 years (=0.016). The results suggest that pS--syn-RBC is increased in MSA patients and can be used as a potential diagnostic biomarker for MSA.
多系统萎缩（MSA）的诊断仍然是一项挑战，因为其症状复杂且与其他帕金森氏症存在重叠。α-突触核蛋白（α-syn）在MSA发病机制中的关键作用使其成为MSA诊断的理想生物标志物。尽管已经广泛评估了脑脊液（CSF）和血浆中α-syn的改变在诊断MSA中的效用，但结果并不一致，可能是由于溶血和其他混杂因素的污染。在本研究中，使用酶联免疫吸附测定法（ELISA）在中国一个由107例MSA患者和220例健康对照组成的队列中测量了红细胞（RBC）中丝氨酸129磷酸化α-syn（pS-α-syn）的水平，这是α-syn的一种主要病理形式。与健康对照相比，MSA患者红细胞中pS-α-syn（pS-α-syn-RBC）水平显著升高（14.02±4.02 ng/mg对11.89±3.57 ng/mg；P<0.0001）。受试者工作特征曲线（ROC）表明 pS-α-syn-RBC能很好地区分患者与对照，灵敏度为80.37%（95%置信区间（CI）：71.58%-87.42%），特异性为88.64%（95%CI：83.68%-92.51%），曲线下面积（AUC）为0.91（95%CI：0.87-0.94）。pS-α-syn-RBC水平与快速眼球运动睡眠行为障碍-香港（RBD-HK）评分呈负相关，且在MSA-P和MSA-C亚型之间存在差异（13.27±1.91对12.19±3.04；P=0.025）。在Hoehn和Yahr分期3期和4期以及发病年龄（AAO）在60至69岁之间观察到亚型之间的差异（P=0.016）。结果表明，MSA患者中pS-α-syn-RBC升高，可作为MSA的潜在诊断生物标志物。
