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

识别帕金森病认知障碍转化的代谢组学标志物

• 批准号: 10557545
• 负责人: Tritia Yamasaki
• 金额: $ 27.54万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557545
• 关键词: Affect; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Amino Acids; Amyloid beta-Protein; Bile Acids; Biological Markers; Blood; Centers of Research Excellence; Cerebrospinal Fluid; Clinic; Clinical; Clinical Trials Design; Cognition; Cognitive; Communities; Consent; Data; Deep Brain Stimulation; Dementia; Deposition; Development; Diagnosis; Disease; Enrollment; Equipment; Essential Tremor; Fatty Acids; Future; Gas Chromatography; Genetic; Goals; Health Care Costs; Healthcare; Impaired cognition; Individual; Kentucky; Lipids; Mass Chromatography; Mass Spectrum Analysis; Measurement; Measures; Metabolic dysfunction; Metabolism; Methods; Mitochondria; Morbidity - disease rate; Movement Disorders; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Operative Surgical Procedures; Parkinson Disease; Parkinson' s Dementia; Participant; Pathologic; Pathology; Pathway interactions; Patients; Persons; Plasma; Population; Preventive therapy; Process; Prognosis; Proteins; Protocols documentation; Publishing; Research; Resources; Sampling; Sphingolipids; Stress; Testing; Therapeutic Intervention; Time; Tissues; Tremor; Universities; Unsaturated Fatty Acids; Work; alpha synuclein; biomarker evaluation; brain tissue; candidate marker; clinical diagnosis; clinical subtypes; cognitive change; cognitive impairment in Parkinson' s; cognitive testing; cost; demented; disorder control; falls; lipidomics; liquid chromatography mass spectroscopy; metabolome; metabolomics; mild cognitive impairment; mortality; motor impairment; multicatalytic endopeptidase complex; neuropathology; non-demented; novel; prognostication; sample collection; tau Proteins; therapeutic target; treatment trial

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.

抽象的 帕金森氏病（PD）是最常见的神经退行性运动障碍，会影响 估计全球有600万人，每年的医疗保健费用超过230亿美元 美国一个人。这笔成本的主要部分是与认知有关的发病率的直接结果 在50-80％的PD患者中发展的损伤。这种发病率似乎是由 蛋白质α-突触核蛋白和阿尔茨海默氏病（AD）相关的病理积累 病理。预测认知障碍发展的能力将影响 PD中预防性疗法的预后，治疗和临床试验设计。目标的目标 项目是确定与PD认知障碍相关的新型代谢标记。这 项目将利用气相色谱质量光谱（GC-MS）和液相色谱 - 评估血液和脑脊液衍生的质谱法（LC-MS）方法 来自没有认知障碍的晚期PD患者的代谢组。然后我们将评估 转化前后从患者手中摄取的血浆的稳态代谢组谱 随着时间的推移，英国 - 阿尔茨海默氏病随着时间的推移养育了认知障碍 研究中心，其中一部分具有神经病理学相关性。这些结果 研究将指导一种更具针对性的方法来进行血浆生物标志物评估 从临床人群中得出的患者中从正常的认知受损转化。这 CNS-MET代谢组学核心的资源对于完成这些目标至关重要 通过评估使用GC-MS和LC-MS的稳态代谢组学。这些研究是 预计将提供新的生物标志物候选者，以预测转化为认知障碍 在PD和未来R01级应用的数据中。