口腔黏膜中的α-突触核蛋白作为多系统萎缩的潜在生物标志物。
Alpha-Synuclein species in oral mucosa as potential biomarkers for multiple system atrophy.
作者信息
Zheng Yuanchu, Cai Huihui, Zhao Jiajia, Yu Zhenwei, Feng Tao
机构信息
Department of Neurology, Center for Movement Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing, China.
出版信息
Front Aging Neurosci. 2022 Oct 11;14:1010064. doi: 10.3389/fnagi.2022.1010064. eCollection 2022.
BACKGROUND
The definitive diagnosis of Multiple system atrophy (MSA) requires the evidence of abnormal deposition of α-Synuclein (α-Syn) through brain pathology which is unable to achieve . Deposition of α-Syn is not limited to the central nervous system (CNS), but also extended to peripheral tissues. Detection of pathological α-Syn deposition in extracerebral tissues also contributes to the diagnosis of MSA. We recently reported the increased expressions of α-Syn, phosphorylated α-Synuclein at Ser129 (pS129), and α-Syn aggregates in oral mucosal cells of Parkinson's disease (PD), which serve as potential biomarkers for PD. To date, little is known about the α-Syn expression pattern in oral mucosa of MSA which is also a synucleinopathy. Here, we intend to investigate whether abnormal α-Syn deposition occurs in oral mucosal cells of MSA, and to determine whether α-Syn, pS129, and α-Syn aggregates in oral mucosa are potential biomarkers for MSA.
METHODS
The oral mucosal cells were collected by using cytobrush from 42 MSA patients (23 MSA-P and 19 MSA-C) and 47 age-matched healthy controls (HCs). Immunofluorescence analysis was used to investigate the presence of α-Syn, pS129, and α-Syn aggregates in the oral mucosal cells. Then, the concentrations of α-Syn species in oral mucosa samples were measured using electrochemiluminescence assays.
RESULTS
Immunofluorescence images indicated elevated α-Syn, pS129, and α-Syn aggregates levels in oral mucosal cells of MSA than HCs. The concentrations of three α-Syn species were significantly higher in oral mucosal cells of MSA than HCs (α-Syn, < 0.001; pS129, = 0.042; α-Syn aggregates, < 0.0001). In MSA patients, the oral mucosa α-Syn levels negatively correlated with disease duration ( = -0.398, = 0.009). The area under curve (AUC) of receiver operating characteristic (ROC) analysis using an integrative model including age, gender, α-Syn, pS129, and α-Syn aggregates for MSA diagnosis was 0.825, with 73.8% sensitivity and 78.7% specificity.
CONCLUSION
The α-Syn levels in oral mucosal cells elevated in patients with MSA, which may be promising biomarkers for MSA.
背景
多系统萎缩（MSA）的确诊需要通过脑病理学检查发现α-突触核蛋白（α-Syn）异常沉积的证据，但这难以实现。α-Syn的沉积不仅局限于中枢神经系统（CNS），还扩展到外周组织。检测脑外组织中病理性α-Syn沉积也有助于MSA的诊断。我们最近报道了帕金森病（PD）口腔黏膜细胞中α-Syn、丝氨酸129位点磷酸化的α-突触核蛋白（pS129）以及α-Syn聚集体的表达增加，它们可作为PD的潜在生物标志物。迄今为止，对于同样属于突触核蛋白病的MSA口腔黏膜中α-Syn的表达模式知之甚少。在此，我们旨在研究MSA患者口腔黏膜细胞中是否存在异常α-Syn沉积，并确定口腔黏膜中的α-Syn、pS129和α-Syn聚集体是否为MSA的潜在生物标志物。
方法
使用细胞刷从42例MSA患者（23例MSA-P型和19例MSA-C型）以及47例年龄匹配的健康对照（HCs）中收集口腔黏膜细胞。采用免疫荧光分析研究口腔黏膜细胞中α-Syn、pS129和α-Syn聚集体的存在情况。然后，使用电化学发光分析法测量口腔黏膜样本中α-Syn种类的浓度。
结果
免疫荧光图像显示，MSA患者口腔黏膜细胞中α-Syn、pS129和α-Syn聚集体水平高于健康对照。MSA患者口腔黏膜细胞中三种α-Syn种类的浓度显著高于健康对照（α-Syn，<0.001；pS129，=0.042；α-Syn聚集体，<0.0001）。在MSA患者中，口腔黏膜α-Syn水平与病程呈负相关（= -0.398，=0.009）。使用包括年龄、性别、α-Syn、pS129和α-Syn聚集体的综合模型进行MSA诊断的受试者操作特征（ROC）分析曲线下面积（AUC）为0.825，灵敏度为73.8%，特异度为78.7%。
结论
MSA患者口腔黏膜细胞中α-Syn水平升高，这可能是MSA有前景的生物标志物。
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