Supplemental for Detection of Glycopeptides of MCI in Patient Serum

摘要：阿尔茨海默病（Alzheimer 's disease， AD）是一种神经退行性疾病，占痴呆的大多数

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.