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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos 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&apos 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&apos 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

项目摘要

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.

抽象的帕金森病 (PD) 是最常见的神经退行性运动障碍，影响据估计，全球有 600 万人，每年的医疗费用超过 230 亿美元仅美国。该成本的主要部分是与认知相关的发病率的直接结果 50-80% 的 PD 患者会出现损伤。这种发病率似乎是由 α-突触核蛋白病理性积累与阿尔茨海默病 (AD) 相关病理学。预测认知障碍发展的能力将会影响 PD 预防性治疗的预后、治疗和临床试验设计。此举的目标该项目旨在鉴定与帕金森病认知障碍相关的新型代谢组学标志物。这项目将利用气相色谱质谱法（GC-MS）和液相色谱法- 质谱 (LC-MS) 方法评估血液和脑脊液来源来自无认知障碍的晚期帕金森病患者的代谢组。然后我们将评估转换为转换前和转换后患者血浆的稳态代谢组图英国阿尔茨海默病长期积累的认知障碍研究中心，其中一部分具有神经病理学相关性。这些结果研究将指导在手术前后进行更有针对性的血浆生物标志物评估方法来自临床人群的患者从正常认知转变为受损认知。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利用 GC-MS 和 LC-MS 评估稳态代谢组学。这些研究是有望提供新的候选生物标志物来预测认知障碍的转化以及未来 R01 级应用的 PD 和数据。