Beta-Amyloid Degradation in CSF as a Biomarker for Alzheimer's Disease

脑脊液中的β-淀粉样蛋白降解作为阿尔茨海默病的生物标志物

• 批准号: 8321439
• 负责人: Samer O. Abdul-Hay
• 金额: $ 6.36万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321439
• 关键词: Age; Alzheimer disease prevention; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Basic Science; Biological Assay; Biological Markers; Brain; Brain region; Catabolism; Cerebrospinal Fluid; Clinic; Clinical; Clinical effectiveness; Cognition; Collaborations; Cysteine; Data; Data Set; Defect; Development; Diagnostic; Disease; Effectiveness; Freezing; Funding; Future; Grant; Hydrolysis; Individual; Intervention; Letters; Liquid substance; Memory; Methods; Minor; Modification; Monitor; Neurodegenerative Disorders; Pathogenesis; Patients; Peptide Hydrolases; Peptides; Pilot Projects; Play; Precipitation; Prevention; Protease Inhibitor; Proteins; Publishing; Relative (related person); Research; Role; Sampling; Serine; Site; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptavidin; Sweden; Symptoms; Therapeutic; Therapeutic Intervention; Time; Universities; Work; aged; base; case control; enzyme activity; improved; inhibitor/antagonist; novel; protein degradation; tau Proteins

DESCRIPTION (provided by applicant): Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by abnormal accumulation of the amyloid b-protein (Ab) in brain regions subserving memory and cognition. Emerging evidence suggests that defects in the proteolytic degradation of Ab may contribute to the pathogenesis of a substantial fraction of idiopathic AD cases, and it is possible that such defects might be detected in clinical samples, particularly the cerebrospinal fluid (CSF). This pilot project seeks to directly determine whether alterations in Ab degradation in CSF might constitute a reliable biomarker for AD. Preliminary results from a small number of samples suggests that Ab catabolism within the CSF of AD patients is significantly reduced relative to age-matched controls. This pilot grant seeks to compare the relative rates of Ab degradation (Aim 1) and the specific site(s) of A2 hydrolysis (Aim 2) in a larger number of CSF samples from AD cases and controls. Furthermore, we will begin to establish the identity of the A2-degrading protease(s) present in CSF through inhibitor profiling (Aim 3). These pilot studies will establish the merit of using CSF A2 catabolism as a biomarker for AD. If successful, the results obtained from this pilot study could be used as the basis for future funding proposals.

描述（由申请人提供）：阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征在于淀粉样蛋白b-蛋白（Ab）在影响记忆和认知的脑区域中的异常积累。新出现的证据表明，抗体的蛋白水解降解的缺陷可能有助于一个相当大的比例的特发性AD病例的发病机制，它是可能的，这样的缺陷可能会在临床样本中检测到，特别是脑脊液（CSF）。该试验项目旨在直接确定CSF中Ab降解的改变是否可能构成AD的可靠生物标志物。来自少量样本的初步结果表明，相对于年龄匹配的对照组，AD患者CSF中的Ab catalase显著降低。该试验资助旨在比较AD病例和对照组大量CSF样本中Ab降解（目标1）的相对速率和A2水解（目标2）的特定位点。此外，我们将开始通过抑制剂谱确定CSF中存在的A2降解蛋白酶的特性（目的3）。这些初步研究将确定使用CSF A2催化剂作为AD生物标志物的优点。如果成功的话，这项试验性研究的结果可作为今后供资建议的基础。