Supplemental for Detection of Glycopeptides of MCI in Patient Serum

摘要：阿尔茨海默病（AD）是一种神经退行性疾病，占痴呆的大多数 病例，影响全球约3000万患者。轻度认知功能障碍（MCI）已被确认 作为晚期AD前临床损害的中间状态。由于AD引发的大脑变化 在出现初始症状之前，例如MCI，需要早期诊断生物标志物 research.然而，由于缺乏明确的诊断方法，AD的早期诊断是一个重大挑战。 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 用于检测这些生物标志物的微创方法。研究表明， 蛋白质中涉及聚糖基团结构变化的糖基化可能作为血清生物标志物是重要的 早期发现各种疾病。我们已经从患者血清中鉴定出这种潜在的糖肽， 其可用于识别早期MCI发展。因此，在拟议的工作中，我们将采用有针对性的 质谱法筛选患者血清中MCI与正常的标志物，基于详细的 聚糖的结构及其位点特异性。这将是基于我们的目标，使用一个多重平行反应 监测（PRM-MS）分析，用于定量检测靶向糖肽，我们可以监测多达50个靶点 标志同时然后，我们将使用潜在的PRM检测进行初步确认研究 糖肽标记物，可以区分正常与MCI患者，并确定性能 基于其灵敏度/特异性的每个标记。这项工作将导致早期阶段的糖肽生物标志物 MCI使用多重PRM-MS方法，其中这些标志物随后可用于进一步的临床研究。 验证。此外，我们还将针对其他神经退行性疾病的样本测试这种方法。

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.