导读： 2018年12月，葛微课题组和人体解剖与组胚学系马超课题组合作在著名的阿尔茨海默症专业期刊Alzheimer & Dementia （IF=12.7）上发表了题为《定量蛋白质组学揭示阿尔茨海默症淀粉状斑块的独特组成》（Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer's disease ）的研究论文。在该研究中，作者通过激光显微切割与高通量定量质谱技术研究了AD人脑、年龄匹配的非AD人脑、以及APP/PS1转基因模型小鼠中APs的蛋白组学特征。

文章链接： https://www.alzheimersanddementia.com/article/S1552-5260(18)33580-5/pdf 

基础所院报道链接：http://sbm.pumc.edu.cn/article/14369 

图1：

      阿尔茨海默症是严重神经退行性疾病，其主要病理学特征是淀粉状斑块(Amyloid Plaques, APs)在脑部的沉积。针对APs研发的药物虽然能够改善模型小鼠的认知水平，在临床实验中并未取得实质性的效果。另一方面，部分认知正常的人脑中也存在APs的沉积。因此，系统性的比较研究APs的组分至关重要。该研究鉴定了40余种高度富集于人脑APs的蛋白组分，并且详细阐述了人脑与模型小鼠脑的异同。研究发现AD模型小鼠脑中多种明显激活的信号通路在人脑中并未发生明显变化，提示其病理机制可能存在不同。该研究为AD病理机制提供了独特见解，也为未来AD诊断及治疗靶点的研发奠定了坚实基础。 

      该研究得到了国家自然科学基金（NSFC＃81271239，＃91632113）、IBMS / CAMS 院长基金（2011RC01）和中国医学科学院医学与健康科技创新工程项目（CIFMS 2016-I2M-1-004）的支持。 

 【摘要】： Introduction: We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer’s disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice. 

Methods: APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labeling coupled high-throughput mass spectra.

Results: Over 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and non-AD APs, including APOE, midkine, VGFR1, and complement C4. Intriguingly, proteins including synaptic structural proteins and complement C1r, C5, and C9 were found to be upregulated in AD APs but not non-AD APs. Moreover, the proteomic pattern of AD APs was distinct from APP/PS1 APs and exhibited some correlation with aging hippocampus.

Discussion: Our results provide new insight into AP composition. We demonstrate unexpected differences between AD, non-AD, and APP/PS1 mouse APs, which may relate to different pathological processes. 

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