Supplemental for Detection of Glycopeptides of MCI in Patient Serum

用于检测患者血清中 MCI 糖肽的补充品

• 批准号: 10492874
• 负责人: David M. Lubman
• 金额: $ 27.45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10492874
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Biological Assay; Biological Markers; Brain; Clinical; Data; Dementia; Detection; Development; Diagnosis; Disease; Early Diagnosis; Glycopeptides; Impairment; Mass Spectrum Analysis; Methods; Monitor; Neurodegenerative Disorders; Patients; Performance; Polysaccharides; Proteins; Reaction; Research; Sampling; Sensitivity and Specificity; Serum; Serum Markers; Site; Specificity; Structure; Symptoms; Testing; Validation; Work; base; detection method; early detection biomarkers; glycosylation; mild cognitive impairment; minimally invasive; patient screening

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder that accounts for the majority of dementia cases, which affects around 30 million patients worldwide. Mild cognitive impairment (MCI) has been recognized as an intermediate state of clinical impairment before advanced AD. Due to changes in the brain triggered by AD before the presentation of initial symptoms, such as for MCI, there is a need for early-stage diagnosis biomarker research. However, early-stage diagnosis of AD represents a significant challenge due to a lack of definitive biomarkers, an overlap of biomarkers with other similar neurodegenerative diseases, and the ability to find minimally invasive methods for detection of these biomarkers. It has been shown that unique changes in glycosylation in proteins that involve structural changes in glycan groups may be important as serum biomarkers for early detection of various diseases. We have identified such potential glycopeptides from patient serum, which may serve to identify early-stage MCI development. In the proposed work we will thus employ a targeted mass spectrometry approach to screen patient serum for markers of MCI versus normal based on the detailed structure of glycans and their site specificity. This will be based on our aim to use a multiplexed Parallel Reaction Monitoring (PRM-MS) assay to quantitatively detect targeted glycopeptides where we can monitor up to 50 target markers simultaneously. We will then demonstrate an initial confirmation study using the PRM assay of potential glycopeptide markers that can discriminate among normal versus MCI patients and determine the performance of each marker based on its sensitivity/specificity. This work will result in glycopeptide biomarkers of early-stage MCI using a multiplexed PRM-MS method where these markers will then be available for further clinical validation. In addition, we will also test this method against samples from other neurodegenerative diseases.

摘要：阿尔茨海默氏病（AD）是一种神经退行性疾病，占痴呆症的大部分 病例，影响了全球约3000万患者。轻度认知障碍（MCI）已被认可 作为高级AD之前的临床障碍中间状态。由于广告触发的大脑变化 在提出初始症状之前，例如MCI，需要早期诊断生物标志物 研究。但是，由于缺乏确定性，AD的早期诊断是一个重大挑战 生物标志物，具有其他类似神经退行性疾病的生物标志物的重叠，以及找到的能力 用于检测这些生物标志物的最小侵入性方法。已经表明，独特的变化 涉及聚糖组结构变化的蛋白质中的糖基化可能很重要，因为血清生物标志物 用于早期发现各种疾病。我们已经从患者血清中确定了这种潜在的糖肽， 这可能有助于识别早期MCI开发。在拟议的工作中，我们将雇用目标 根据详细的 聚糖的结构及其场地特异性。这将基于我们使用多重平行反应的目标 监测（PRM-MS）测定法以定量检测靶向糖肽，我们可以监视多达50个目标 简单的标记。然后，我们将使用潜在的PRM测定法证明初始确认研究 可以区分正常患者并确定性能的糖肽标记物 每个标记的灵敏度/特异性。这项工作将导致早期糖肽生物标志物 MCI使用多重PRM-MS方法，然后将这些标记可用于进一步的临床 验证。此外，我们还将针对其他神经退行性疾病的样品测试此方法。