Peptide Biomarkers for Parkinson Disease

帕金森病的肽生物标志物

基本信息

批准号：
9191379
负责人：
Jing Zhang
金额：
$ 53.13万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9191379
关键词：
Address Affect Alzheimer&apos s Disease American Anosmia Antibodies Biological Assay Biological Markers Blood Body Fluids Caring Cells Cerebrospinal Fluid Clinical Collaborations Cross-Sectional Studies Data Detection Development Diagnosis Differential Diagnosis Disease Disease Progression Early Diagnosis Elderly Family Goals Human Image LRRK2 gene Longitudinal cohort Mass Spectrum Analysis Medical Monitor Multiple System Atrophy Mutation Neural Cell Adhesion Molecule L1 Neuraxis Neurodegenerative Disorders Organ Parkinson Disease Parkinsonian Disorders Pathogenesis Patient Recruitments Patients Pennsylvania Peptides Performance Persons Pharmaceutical Preparations Pilot Projects Plasma Population Process Progressive Supranuclear Palsy Proteins Proteomics Quality of life Reaction Reproducibility Research Research Design Resources Risk Sampling Sensitivity and Specificity Severity of illness Societies Symptoms Techniques Testing Tocopherols Transportation Universities Validation Variant Washington Work accurate diagnosis alpha synuclein base biomarker discovery biomarker identification biomarker panel blood-based biomarker body system cohort cost deprenyl design diagnostic biomarker disease diagnosis disorder control exosome hyposmia improved microvesicles parkin gene/protein pre-clinical progression marker public health relevance tau Proteins treatment effect

项目摘要

DESCRIPTION (provided by applicant): Objective, reliable, and reproducible biomarkers are clearly needed to assist with accurate diagnosis of Parkinson disease (PD), especially at early stages, as well as for facilitating differential diagnosis and disease monitoring. The proposal is designed to meet several major challenges of current biomarker research, specifically: 1) significant variations associated with antibody-based protein assays, 2) low sensitivity and specificity of blood based markers, and 3) detection of PD at early stages. To address the problems of antibody-based assays, our strategy is development of targeted mass spectrometry-based techniques, such as selected reaction monitoring (SRM), to identify unique peptide markers derived from proteins either showing promise in previous proteomics profiling, or known to be critical to PD pathogenesis, e.g., α-synuclein, parkin and LRRK2, in human cerebrospinal fluid (CSF). To facilitate discovery and validation of blood based biomarkers, a specific population of central nervous system derived plasma exosomes, the cargo-carrying microvesicles recognized recently to transport biomolecules among different cells or organ systems, will be isolated before SRM analysis. The unique peptide markers will be tested in several large, well-established cohorts, e.g., Udall Centers affiliated with the University of Washington and University of Pennsylvania, DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) and PPMI (Parkinson Progression Marker Initiative), with cross-sectional and longitudinal samples collected, along with extensive clinical characterization. Finally, to improve early diagnosis, we will make use of two cohorts consisting of subjects at elevated risk for PD (i.e., asymptomatic subjects with LRRK2 mutations or anosmia/hyposmia), with the goal of discovering biomarkers capable of identifying subjects with early or premotor PD. The studies designed for this project, if successful, have the potential to result in a panel(s of biomarkers that are robust, with less variation than can currently be achieved, and in a body fluid that is readily accessible in a regular clinical setting. Markers for early diagnosis and progression of PD are critical in understanding how to arrest or slow PD progression.

描述（由适用提供）：显然需要客观，可靠和可重复的生物标志物来帮助对帕金森氏病（PD）进行准确的诊断，尤其是在早期阶段，以及支持差异诊断和疾病监测。该提案旨在应对当前生物标志物研究的几个主要挑战，特别是：1）与基于抗体的蛋白质测定相关的显着变化，2）2）低灵敏度和基于血液标记的特异性，以及3）在早期阶段检测PD。 To address the problems of antibody-based assessments, our strategy is development of targeted mass spectrometry-based techniques, such as selected reaction monitoring (SRM), to identify unique peptide markers derived from proteins either showing promise in previous proteomics profiling, or known to be critical to PD pathogenesis, e.g., α-synuclein, parkin and LRRK2, In human cerebrospinal fluid (CSF).为了促进基于血液的生物标志物的发现和验证，特定的中枢神经系统衍生血浆外泌体的特定群体将在SRM分析之前分离出最近公认用于在不同细胞或器官系统之间运输生物分子的货运微泡。独特的肽标志物将在几个大型，完善的同类群体中进行测试，例如，Udall中心与华盛顿大学和宾夕法尼亚大学（DataTop表征。最后，为了改善早期诊断，我们将利用两个人群，这些人群由PD风险升高（即患有LRRK2突变或厌食症/低质量的非对称受试者）组成，目的是发现能够鉴定出具有早期或预耐力PD受试者的生物标志物。为该项目设计的研究，如果成功的话，有可能导致面板（生物标志物的稳定性，差异少于目前所能实现的差异，并且在常规临床环境中易于使用的体液。早期诊断和PD的标记PD在理解如何抑制或减慢PD进展方面至关重要。