运动前期帕金森病唇腺α-突触核蛋白的生物学标记物研究

Parkinson’s disease (PD) is a common neurodegenerative disease. Premotor PD is phase during which nonmotor clinical features as well as physiological abnormalities may be present. Patients with premotor PD have nonmotor symptoms such as decreased sense of smell, depression, and various gastrointestinal and other systemic features that have been shown to predate the classical motor features of PD. These premotor markers could be used to screen for PD before motor abnormalities are present. However, there are no diagnosis criteria for premotor PD and it is hard to make the diagnosis. .Recently, some researches provide us evidence that peripheral nervous system (PNS) has also been affected by Lewy body pathology, including skin, enteric nervous system and salivary gland. Our study is gonging to enroll 60-100 premotor PD patients and 60-100 controls to test whether these is α-synuclein deposition in minor salivary gland and its existence form. At the same time, the level of α-synuclein in saliva and red blood cell is also tested to compare with that in minor salivary gland. Our aim is to improve the capacity of pathological diagnosis for premotor PD. And we expect that this method could be the cornerstone of early diagnosis and early intervention.

帕金森病（Parkinson’s disease，PD）是一种常见的中老年神经系统退行性疾病。.运动前期PD指在出现典型运动障碍症状之前，已经存在病理改变和非运动症状（嗅觉减退、便秘、睡眠行为异常、抑郁）。早期诊断运动前期PD对早期治疗、改善预后具有重要意义。目前运动前期PD尚缺乏特异性的生物标记物，诊断困难。传统观点认为PD特征性病理变化仅存在于中枢神经系统，新近研究发现运动障碍期PD患者外周组织中（皮肤、唾液腺、肠道、心脏等部位的自主神经纤维以及交感神经干）也存在特征性的ɑ-突触核蛋白异常聚集。本研究拟收集运动前期PD患者60-100名，对照组60-100名，对其进行唇腺活检，观察是否存在ɑ-突触核蛋白异常聚集，并检测其存在形式，验证这种病理改变在运动前期PD中是否具有普遍性和特征性，及其是否可以作为运动前期PD的外周病理诊断标志物。同时与血液红细胞、唾液中ɑ-突触核蛋白水平进行对比，提高运动前期PD的活检病理诊断水平，为早期诊断、早期治疗奠定基础。

帕金森病（Parkinson’s disease，PD）是一种常见的中老年神经系统退行性疾病。早期诊断PD对早期治疗、改善预后具有重要意义，而目前早期PD尚缺乏特异性的生物标记物，诊断困难。传统观点认为PD特征性病理变化仅存在于中枢神经系统，新近研究发现运动障碍期PD患者外周组织和血液系统中（皮肤、唾液腺、心脏等部位的自主神经纤维以及交感神经干）也存在特征性的ɑ-突触核蛋白异常聚集。本研究收集早期PD患者75名，多系统萎缩（MSA）患者 70名 ，健康对照组133名，收集临床数据和唇腺、唾液、血液样本收集，建立运动前期及早期帕金森病人临床数据库和样本库，同时应用国际认可的高灵敏的电化学发光免疫法（MSD）、免疫组化方法对不同标本进行α-突触核蛋白及其蛋白修饰产物检测、脑多巴胺转运体代谢显像和参数图分析。探索发现唇腺硝基化ɑ-突触核蛋白、唾液外泌体和红细胞胞膜ɑ-突触核蛋白在辅助诊断早期PD方面均具有普遍性和特征性，可以作为潜在的早期PD的外周病理诊断标志物，该研究结果可辅助医生进行早期PD临床诊断，为早期治疗奠定基础，具有一定的临床转化意义。同时对早期PD的病理机制的探索依据有一定的提示作用。