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：阿尔茨海默病（AD）是一种神经退行性疾病，占痴呆的大部分。 已确认影响全球约 3000 万患者的轻度认知障碍 (MCI)。 由于 AD 引发的大脑变化，是晚期 AD 之前临床损伤的中间状态。 在出现初始症状（例如 MCI）之前，需要早期诊断生物标志物 然而，由于缺乏明确的证据，AD 的早期诊断面临着巨大的挑战。 生物标志物，生物标志物与其他类似神经退行性疾病的重叠，以及发现的能力 检测这些生物标志物的微创方法已被证明具有独特的变化。 涉及聚糖基团结构变化的蛋白质糖基化可能作为血清生物标志物很重要 我们已经从患者血清中鉴定出此类潜在的糖肽， 这可能有助于确定早期 MCI 发展。因此，在拟议的工作中，我们将采用有针对性的方法。 质谱法根据详细信息筛选患者血清中 MCI 标记物与正常标记物 聚糖的结构及其位点特异性这将基于我们使用多重平行反应的目标。 监测 (PRM-MS) 测定可定量检测目标糖肽，我们可以监测多达 50 个目标 然后，我们将使用 PRM 潜力分析进行初步确认研究。 糖肽标记物可区分正常患者与 MCI 患者并确定其表现 根据其敏感性/特异性对每个标记进行分析，这项工作将产生早期的糖肽生物标记。 MCI 使用多重 PRM-MS 方法，然后这些标记物将可用于进一步的临床 此外，我们还将针对其他神经退行性疾病的样本测试该方法。