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

摘要 帕金森氏病（PD）是最常见的神经退行性运动障碍， 估计全球有600万人，每年的医疗保健费用超过230亿美元， 美国独自。这一成本的主要部分是与认知相关的发病率的直接结果。 在50-80%的PD患者中发生的损害。这种发病率似乎是由 蛋白质α-突触核蛋白的病理积累和阿尔茨海默病（AD）相关 病理学预测认知障碍发展的能力将对 PD预防性治疗的预后、治疗和临床试验设计。这个目标 项目是确定新的代谢组学标志物与认知障碍的PD。这 该项目将利用气相色谱质谱（GC-MS）和液相色谱- 质谱（LC-MS）方法，以评估血液和脑脊液来源的 来自无认知障碍的晚期PD患者的代谢组。我们将评估 在转换为前和转换后从患者采集的血浆的稳态代谢组学特征 认知障碍，这已被银行随着时间的推移，由英国-阿尔茨海默氏病 研究中心，其中一部分有神经病理相关性。的结果予以 研究将指导一种更有针对性的方法，在治疗前后进行血浆生物标志物评价。 从临床人群中抽取的患者从正常认知到受损认知的转换。的 CNS-Met代谢组学核心的资源对于完成这些目标至关重要 通过利用GC-MS和LC-MS评估稳态代谢组学。这些研究是 有望为预测向认知障碍的转化提供新的生物标志物候选物 用于未来R 01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.