Identifying Metabolomic Markers in Conversion to Cognitive Impairment in Parkinson's Disease

摘要 帕金森病(PD)是最常见的神经退行性运动障碍，影响 估计全球有600万人，每年的医疗成本超过230亿美元 仅美国一国。这一成本的很大一部分是与认知相关的发病率的直接结果 在50-80%的帕金森病患者中出现的损害。这种发病率似乎是由 α-突触核蛋白的病理性积聚与阿尔茨海默病(AD)相关 病理学。预测认知障碍发展的能力将对 帕金森病预防性治疗的预后、治疗和临床试验设计。这样做的目的是 项目是寻找与帕金森病认知障碍相关的新的代谢组学标记物。这 该项目将利用气相色谱-质谱仪(GC-MS)和液相色谱- 液质联用(LC-MS)分析血液和脑脊液来源 无认知障碍的晚期帕金森病患者的代谢组。然后我们将评估 转流前后患者血浆的稳态代谢谱 英国长期积累的认知障碍--阿尔茨海默氏症 研究中心，其中一部分与神经病理相关。这些研究的结果 研究将指导一种更有针对性的方法在治疗前后评估血浆生物标志物 从临床人群中抽取的患者从正常到认知受损的转变。这个 CNS-Met代谢组学核心资源将是实现这些目标的关键 通过GC-MS和LC-MS对稳态代谢组学的评价。这些研究是 有望为预测转化为认知障碍提供新的生物标志物候选 用于未来R01级应用的PD和数据。

ABSTRACT Parkinson's disease (PD), the most common neurodegenerative movement disorder, affects an estimated six million people worldwide and costs over $23 billion annually in healthcare costs in the US alone. A major portion of this cost is a direct result of the morbidity related to cognitive impairment that develops in 50-80% of PD patients. This morbidity appears to be driven by pathologic accumulation of the protein alpha-synuclein and Alzheimer disease (AD)-related pathologies. The ability to predict the development of cognitive impairment would have impact on prognosis, treatment, and clinical trial design for preventative therapies in PD. The goal of this project is to identify novel metabolomic markers associated with cognitive impairment in PD. This project will utilize gas chromatography mass-spectroscopy (GC-MS) and liquid chromatography- mass spectroscopy (LC-MS) methods to assess the blood- and cerebrospinal fluid-derived metabolome from advanced PD patients without cognitive impairment. We will then assess steady-state metabolomic profiles of plasma taken from patients before and after conversion to cognitive impairment which have been banked over time by the UK-Alzheimer's Disease Research Center, a portion of which have neuropathological correlation. The results of these studies will guide a more targeted approach to plasma biomarker evaluation before and after the conversion from normal to impaired cognition in patients drawn from the clinic population. The resources of the CNS-Met Metabolomics Core will be essential to the completion of these aims via assessment of steady-state metabolomics utilizing GC-MS and LC-MS. These studies are expected to provide new biomarker candidates for predicting conversion to cognitive impairment in PD and data for future R01-level applications.