纵向队列中帕金森病特异性蛋白生物标志物的筛选与血清预警/诊断模型的建立

帕金森病( PD)是一种神经系统退行性疾病，诊断主要依赖病史、临床症状及体征等。而帕金森病病人只有在多巴胺能神经元变性缺失 50%-70%以上方出现临床症状，这使患者错失了早期诊断、治疗及预防干预的机会。因此寻找可检测的生物标志物，早期诊断并跟踪疾病的进展成为目前研究的热点。本研究拟在1986年建立的林县营养干预队列中，比较2000年队列随访中确诊的帕金森病病例与正常人群在进入队列时(1986年)和疾病诊断时（2000年）的蛋白质差异表达谱，筛选并鉴定可能发挥重要作用的蛋白生物标志物，建立帕金森病预警模型和诊断模型。同时纵向分析帕金森病病例与正常人群进入队列时、确诊时与本项目开展后随访时三个时相血清样本的蛋白指纹图谱，观察不同时间位点蛋白生物标志物的变化，并分析其对疾病长期预后的影响。本研究结果将为寻找PD早期诊断的生物标记物和进一步揭示帕金森病病理过程、寻找药物治疗的靶点提供依据。

Parkinson's disease (PD) is a neurodegenerative disease which diagnosis mainly depends on the medical history, clinical symptoms and signs. But the clinical symptoms won't be appeared until dopaminergic neurons of more than 50%-70% have been degenerated, thus usually makes the PD patients to miss opportunities of the early diagnosis, early treatment and intervention. Therefore, looking for the biomarkers of early diagnosis and tracking the progression of the disease become hot spots of current research. In this project, the effort will be given to screen some new biomarkers which could be used for diagnosis in the PD's early phase or tracking the PD's progression. So far, the Serum samples from the intervention nutrition cohort population established in LinXian county in 1986 (baseline study) have been available to be used to build up a database of protein expression as well as their follow-up study (established in 2000), and their future samples (planned in 2013). Then, the differences of protein expression between PD case and control will be analyzed. Hopefully, a Parkinson's disease early prediction model and a diagnosis model will be established in this project. Furthermore, the longitudinal change of protein biomarkers will be observed and their influence on long-term prognosis for PD will be analyzed among three-phase serum samples which are baseline time(1986)、diagnostic time(2000) and follow-up time(2013) in this study. So serum protein fingerprints will be obtained and the alteration of the biomarkers established in this project will be observed. The results obtained in this project will provide the basis to screen specific PD biomarkers of early diagnosis, and it is also helpful to reveal pathologic process and get some treatment targets of PD.