基于iTRAQ技术的阿尔茨海默病早期诊断血液生物标志物研究

Alzheimer’s disease (AD) is the most common type of senile dementia. Currently, there is no effective treatment available. Early diagnosis of AD is crucial for delaying the development of disease and improving patient quality of life. At present, there is still a clinical need for a sensitive, specific, easily accessible biomarker. Recent studies indicate that some specific proteins in blood are potential biomarkers of AD. Previously, we had collected serum samples from AD patients and carried out APOE genotyping. In this research, we intend to obtain proteomic expression profiles of MCI, AD and cognitively normal subjects and identify a set of differentially expressed proteins using iTRAQ quantitative proteomics. Furthermore, we will validate these proteins in individual samples by Western blot and ELISA to screen candidate biomarkers with high sensitivity and specificity for AD. In addition, the correlation between objective biomarkers and APOE genotypes will be explored. Finally, combined with bioinformatics analysis, the molecular functions of biomarkers and their effects on AD progression will be discussed. We aim to develop a novel method using serum biomarkers for the early diagnosis of AD. This research will provide theoretical and experimental evidences for the elucidation of pathological progression of AD, as well as novel indicators and targets for early diagnosis, intervention and treatment of AD and evaluation of new drugs.

阿尔茨海默病（AD）是老年痴呆症最主要的类型，临床上尚缺乏有效的防治方法。AD的早期精确诊断对于延缓病情发展和提高患者的生活质量非常关键，目前仍缺乏简单易行、敏感性和特异性均较高的生物标志物。最新研究显示，血液中存在AD特异性的蛋白质。本项目拟在前期收集的AD患者样本和APOE基因分型检测的基础上，利用iTRAQ定量蛋白质组技术建立MCI患者、AD患者与正常对照者的蛋白质表达谱，筛选出与AD相关的差异表达蛋白，然后利用Western Blot和ELISA进行临床验证，进一步筛选出具有一定敏感性和特异性的目标蛋白标志物，分析其与APOE基因型的相关性，并结合生物信息学分析探讨其生物学功能及在AD发生发展中的作用，有望建立新的基于血清蛋白质的AD早期诊断方法。本项目的实施将为阐明AD的病理进程提供理论和实验依据，为AD早期精确诊断、干预治疗及新药评价提供新指标与新靶点。