基于液质联用蛋白质组学技术的阿尔茨海默病血清生物标志物及生物信息学研究  

Serum biomarkers and bioinformatics of Alzheimer’s disease based on LC-MS/MS proteomics

作　　者：许婷婷[1] 郭鹏[2] 张巍[2] 王晓良[1] XU Ting-ting;GUO Peng;ZHANG Wei;WANG Xiao-liang(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Neurology Center,Beijing Tian Tan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050 [2]首都医科大学附属北京天坛医院,神经病学中心,北京100070

出　　处：《药学学报》2020年第7期1604-1613,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81573417)。

摘　　要：为了寻找有效的阿尔茨海默病(Alzheimer’s disease,AD)血液生物标志物,本研究采用非标记液相色谱-串联质谱技术对AD患者和健康对照受试者(healthy control subjects,HC)的血清进行比较蛋白质组学分析,成功鉴定到387个蛋白,其中61个蛋白是显著变化的。基因本体(gene ontology,GO)富集分析结果显示,一些与AD发病有关的GO功能条目在差异蛋白中显著富集,包括胆固醇和脂质代谢、炎症反应、凝血和止血过程以及免疫反应等生物学过程。因此,根据上述结果和蛋白在8个比较组中含量变化的一致性程度,共选取了18个蛋白作为AD候选生物标志物。蛋白-蛋白相互作用结果提示这18个蛋白与淀粉样β(A4)前体蛋白[amyloid beta(A4)precursor protein,APP]都具有直接或间接的作用,因此,推测这些蛋白表达水平或功能的改变可能会影响淀粉样蛋白(amyloid-β,Aβ)代谢和参与AD的发生,具有成为AD血液生物标志物的潜能。To identify potential serum proteins that might serve as biomarkers for Alzheimer’s disease(AD),we performed comparative proteomic profiling of sera from AD and healthy control subjects using label-free LC-MS/MS.Our study identified 387 proteins,61 of which showed significant changes in the serum of AD patients compared to healthy controls.Gene ontology(GO)enrichment analysis showed that some GO terms related to the pathogenesis of AD were significantly enriched in differentially expressed proteins,including cholesterol and lipid metabolism,inflammation,coagulation and hemostasis processes,and immune responses.Therefore,based on the above results and the consistency of protein content changes in the 8 comparison groups,18 proteins were selected as candidate biomarkers.Protein-protein interaction results suggest that these 18 proteins can directly or indirectly interact with APP.Therefore,changes in the levels or functions of these proteins may affect Aβmetabolism and participate in the occurrence of AD,and have the potential to become AD blood biomarkers.

关 键 词：阿尔茨海默病 生物标志物 血清 非标记液相色谱-串联质谱法 蛋白质组学 

分 类 号：R963[医药卫生—微生物与生化药学]