英国剑桥大学Sjors H. W. Scheres、Michel Goedert等研究人员合作建立基于结构的tau病分类。相关论文于2021年9月29日在线发表在《自然》杂志上。

研究人员发现，来自进行性核上性麻痹（PSP）的tau丝结构定义了一个新的三层折叠。此外，球状胶质性tau病的tau丝结构与PSP的tau丝结构相似。嗜银颗粒病（AGD）的tau丝折叠不同，而是类似于皮质基底层变性的四层折叠。AGD的折叠也在与年龄有关的tau星形胶质病中观察到。来自MAPT（微管相关蛋白tau基因）内含子10的+3或+16位突变遗传病例的tau原丝结构也与AGD的原丝结构相同，这表明四重复tau的相对过度生产可引起AGD的折叠。最后，来自英国家族性痴呆和丹麦家族性痴呆病例的tau丝结构与阿尔茨海默病和原发性年龄相关性tau病病例的tau丝结构相同。

这些发现表明，可根据丝状结构对tau病理进行分层分类，这对临床诊断和神经病理学是一种补充，同时也可以确定新的结构——如研究人员所展示的一个被诊断为PSP的病例，但其丝状结构介于球状胶质tau病和PSP之间。

据介绍，tau蛋白有序地组装成丝状物是几种神经退行性疾病的特征，这些疾病被称为tau病。以前有报道说，通过冷冻电镜，阿尔茨海默氏病、皮克氏病、慢性创伤性脑病和皮质基底层变性的tau丝结构是不同的。

附：英文原文

Title: Structure-based classification of tauopathies

Author: Shi, Yang, Zhang, Wenjuan, Yang, Yang, Murzin, Alexey G., Falcon, Benjamin, Kotecha, Abhay, van Beers, Mike, Tarutani, Airi, Kametani, Fuyuki, Garringer, Holly J., Vidal, Ruben, Hallinan, Grace I., Lashley, Tammaryn, Saito, Yuko, Murayama, Shigeo, Yoshida, Mari, Tanaka, Hidetomo, Kakita, Akiyoshi, Ikeuchi, Takeshi, Robinson, Andrew C., Mann, David M. A., Kovacs, Gabor G., Revesz, Tamas, Ghetti, Bernardino, Hasegawa, Masato, Goedert, Michel, Scheres, Sjors H. W.

Issue&Volume: 2021-09-29

Abstract: The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the structures of tau filaments from Alzheimer’s disease1,2, Pick’s disease3, chronic traumatic encephalopathy4 and corticobasal degeneration5 are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a new three-layered fold. Moreover, the structures of tau filaments from globular glial tauopathy are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs, instead resembling the four-layered fold of corticobasal degeneration. The AGD fold is also observed in ageing-related tau astrogliopathy. Tau protofilament structures from inherited cases of mutations at positions +3 or +16 in intron 10 of MAPT (the microtubule-associated protein tau gene) are also identical to those from AGD, suggesting that relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, the structures of tau filaments from cases of familial British dementia and familial Danish dementia are the same as those from cases of Alzheimer’s disease and primary age-related tauopathy. These findings suggest a hierarchical classification of tauopathies on the basis of their filament folds, which complements clinical diagnosis and neuropathology and also allows the identification of new entities—as we show for a case diagnosed as PSP, but with filament structures that are intermediate between those of globular glial tauopathy and PSP.

DOI: 10.1038/s41586-021-03911-7

Source: https://www.nature.com/articles/s41586-021-03911-7