泛神经变性蛋白质组学揭示疾病亚型和分子特征，这一成果由圣犹达儿童研究医院彭隽敏团队经过不懈努力而取得。这一研究成果发表在2026年3月23日出版的国际学术期刊《细胞》上。
研究团队通过对2279个人脑样本的多层深度蛋白质组学分析，绘制了一幅泛神经变性图谱（PanNDA），涵盖6种主要的神经变性：阿尔茨海默病（AD）、路易体痴呆（LBD）、伴TDP-43病理的额颞叶变性、伴tau病理的进行性核上性麻痹、血管性痴呆和帕金森病。PanNDA整合了来自整个蛋白质组、洗涤剂不溶性蛋白质组和翻译后修饰（磷酸化和泛素化）的数据，实现了疾病内和疾病间的比较。
疾病内部分析揭示了不同的分子亚型（例如，AD中有3种，LBD中有4种），揭示了失调的途径，并优先考虑了排名最高的蛋白质。疾病间比较确定了NDs的共同改变，例如GPNMB在小胶质细胞和溶酶体活化中，NPTX2在突触调节中，以及蛋白质网络中的疾病特异性变化和中枢调节因子。总的来说，PanNDA为理解ND机制提供了一个系统级框架，并作为一个基础抵抗，可通过一个交互式网站：https://penglab.shinyapps.io/pannda访问。
据了解，神经退行性疾病由于其复杂性和分子异质性给临床带来了挑战。
附：英文原文
Title: Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures
Author: Him K. Shrestha, Huan Sun, Jay M. Yarbro, DongGeun Lee, Danting Liu, Erming Wang, Meghan McReynolds, Nan Zhang, Boer Xie, Shu Yang, Kaiwen Yu, Suresh Poudel, Yuxin Li, Zuo-Fei Yuan, Dehui Kong, Minghui Wang, Zhen Wang, Mingming Niu, Hong Wang, Masihuz Zaman, Ju Wang, David R. Vanderwall, Yu Sun, Zhiping Wu, Ping-Chung Chen, Bing Bai, Anthony A. High, Júlia Faura, Chunyu Liu, David A. Bennett, Erik C.B. Johnson, Nicholas T. Seyfried, Allan I. Levey, Vahram Haroutunian, Geidy E. Serrano, Thomas G. Beach, Michael DeTure, Takahisa Kanekiyo, Ronald C. Petersen, Guojun Bu, Pamela J. McLean, Dennis W. Dickson, Rosa Rademakers, Gang Yu, Xusheng Wang, Bin Zhang, Junmin Peng
Issue&Volume: 2026-03-23
Abstract: Neurodegenerative diseases (NDs) pose clinical challenges due to their complexity and molecular heterogeneity. Here, we present a pan-neurodegeneration atlas (PanNDA) from multilayer, deep proteomic analysis of 2,279 human brain samples spanning 6 major NDs: Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal lobar degeneration with TDP-43 pathology, progressive supranuclear palsy with tau pathology, vascular dementia, and Parkinson’s disease. PanNDA integrates data from whole proteome, detergent-insoluble proteome, and posttranslational modifications (phosphorylation and ubiquitination), enabling intra- and inter-disease comparisons. Intra-disease analyses uncover distinct molecular subtypes (e.g., three in AD and four in LBD), reveal dysregulated pathways, and prioritize top-ranked proteins. Inter-disease comparisons identify shared alterations in NDs, such as GPNMB in microglial and lysosomal activation and NPTX2 in synaptic regulation, alongside disease-specific changes and hub regulators within protein networks. Overall, PanNDA provides a systems-level framework for understanding ND mechanisms and serves as a foundational resource that is accessible via an interactive website: https://penglab.shinyapps.io/pannda.
DOI: 10.1016/j.cell.2026.02.026
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00233-3