小柯机器人

美国埃默里大学医学院Nicholas T. Seyfried和Erik C. B. Johnson小组，通过对阿尔茨海默氏病（AD）患者的大脑和脑脊液进行大规模蛋白质组学分析，揭示了与小胶质细胞和星形胶质细胞激活相关的早期能量代谢变化。这一研究成果于2020年4月13日在线发表在《自然—医学》杂志上。

研究人员使用定量质谱法和共表达网络分析的方法进行了迄今为止与AD相关的最大蛋白质组学研究。与糖代谢有关的蛋白质网络模块已成为与AD病理学和认知障碍最相关的模块之一。该模块富含AD遗传危险因素以及与抗炎状态相关小胶质细胞和星形胶质细胞的蛋白质标志物，表明其具有的生物学功能在AD中起保护作用。

在疾病的早期阶段，该模块的蛋白质表达在脑脊髓液中升高。通过定量蛋白质组学对2000多个大脑样本和近400个脑脊液样本进行的研究，研究人员确定了AD大脑中的蛋白质和生物过程，其可能成为治疗该疾病的靶点和流体生物标志物。

附：英文原文

Title: Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation

Author: Erik C. B. Johnson, Eric B. Dammer, Duc M. Duong, Lingyan Ping, Maotian Zhou, Luming Yin, Lenora A. Higginbotham, Andrew Guajardo, Bartholomew White, Juan C. Troncoso, Madhav Thambisetty, Thomas J. Montine, Edward B. Lee, John Q. Trojanowski, Thomas G. Beach, Eric M. Reiman, Vahram Haroutunian, Minghui Wang, Eric Schadt, Bin Zhang, Dennis W. Dickson, Nilfer Ertekin-Taner, Todd E. Golde, Vladislav A. Petyuk, Philip L. De Jager, David A. Bennett, Thomas S. Wingo, Srikant Rangaraju, Ihab Hajjar, Joshua M. Shulman, James J. Lah, Allan I. Levey, Nicholas T. Seyfried

Issue&Volume: 2020-04-13

Abstract: Our understanding of Alzheimer’s disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly associated with AD pathology and cognitive impairment. This module was enriched in AD genetic risk factors and in microglia and astrocyte protein markers associated with an anti-inflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were elevated in cerebrospinal fluid in early stages of the disease. In this study of >2,000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brains that may serve as therapeutic targets and fluid biomarkers for the disease.

DOI: 10.1038/s41591-020-0815-6

Source: https://www.nature.com/articles/s41591-020-0815-6

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex