上海交通大学李丹小组开发出TPPP/p25淀粉样蛋白播种活性作为多系统萎缩的特异性生物标志物。2026年5月26日，国际知名学术期刊《细胞》发表了这一成果。
研究组报道微管蛋白聚合促进蛋白（TPPP/p25）作为多系统萎缩（MSA）特异性诊断的脑脊液（CSF）生物标志物。研究人员证明了原生TPPP/p25对淀粉样蛋白聚集具有自我保护作用，而疾病相关突变破坏了这种保护作用，触发TPPP/p25聚集。低温电子显微镜（cryo-EM）分析显示，折叠良好的核心结构域（CORE）经历了很大的构象变化来介导淀粉样蛋白的形成。
基于这一见解，课题组人员开发了一种以最小化CORE （miniCORE）为主题的种子扩增实验，该实验可以检测脑脊液中的TPPP/p25淀粉样蛋白种子，并能有效区分MSA与帕金森病（PD）和其他神经退行性疾病。他们的研究结果证实，错误折叠的TPPP/p25是一种有前景的、特异性的生物标志物，可用于MSA诊断。
据介绍，人体液中α-突触核蛋白（α-syn）淀粉样蛋白种子的检测在突触核蛋白病的临床诊断中引起了极大的兴趣。然而，作为一种常见的生物标志物，α-syn在可靠区分不同疾病方面缺乏特异性。
附：英文原文
Title: TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy
Author: Shuyi Zeng, Shenqing Zhang, Shengnan Zhang, Yun Fan, Wencheng Xia, Feiyang Chen, Chengan Huang, Shiran Lv, Jinxia Lu, Yunpeng Sun, Kaien Liu, Yunxia Li, Yaoyang Zhang, Jian Wang, Cong Liu, Dan Li
Issue&Volume: 2026-05-26
Abstract: Detection of α-synuclein (α-syn) amyloid seeds in human biofluids has attracted great interest for clinical diagnosis of synucleinopathies. However, as a common biomarker, α-syn lacks specificity in reliably differentiating distinct disorders. Here, we report tubulin polymerization promoting protein (TPPP/p25) as a cerebrospinal fluid (CSF) biomarker for the specific diagnosis of multiple system atrophy (MSA). We demonstrate that native TPPP/p25 is self-protected against amyloid aggregation, while disease-related mutation disrupts this protection, triggering TPPP/p25 aggregation. Cryo-electron microscopy (cryo-EM) analysis reveals that the well-folded core domain (CORE) undergoes large conformational changes to mediate amyloid formation. Based on this insight, we developed a seed amplification assay using a minimized CORE (miniCORE) monomer, which detects TPPP/p25 amyloid seeds in CSF and robustly differentiates MSA from Parkinson’s disease (PD) and other neurodegenerative diseases. Our findings establish misfolded TPPP/p25 as a promising, specific biomarker in biofluids for MSA diagnosis.
DOI: 10.1016/j.cell.2026.04.050
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00517-9