First identified in 1975, tau was implicated in Alzheimer's disease 10 years later. Filamentous tangle inclusions were known to be made of hyperphosphorylated tau by 1991, with similar inclusions gaining recognition for being associated with other neurodegenerative diseases. In 1998, mutations in MAPT, the gene that encodes tau, were identified as the cause of a dominantly inherited form of frontotemporal dementia with abundant filamentous tau inclusions. While this result indicated that assembly of tau into aberrant filaments is sufficient to drive neurodegeneration and dementia, most cases of tauopathy are sporadic. More recent work in experimental systems showed that filamentous assemblies of tau may first form in one brain area, and then spread to others in a prion-like fashion. Beginning in 2017, work on human brains using high-resolution techniques has led to a structure-based classification of tauopathies, which has opened the door to a better understanding of the significance of tau filament formation.

中文翻译：

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Tau蛋白与神经退行性变

tau 蛋白于 1975 年首次被发现，10 年后被认为与阿尔茨海默病有关。1991 年，人们知道丝状缠结内含物是由过度磷酸化的 tau 蛋白构成的，类似的内含物因与其他神经退行性疾病相关而获得认可。1998 年，编码tau 蛋白的基因MAPT的突变被确定为显性遗传性额颞叶痴呆的病因，该痴呆具有丰富的丝状 tau 蛋白包涵体。虽然这一结果表明 tau 蛋白组装成异常丝足以导致神经变性和痴呆，但大多数 tau 蛋白病病例是散发性的。最近在实验系统中的研究表明，tau 蛋白的丝状组装可能首先在一个大脑区域形成，然后以类似朊病毒的方式扩散到其他区域。从 2017 年开始，使用高分辨率技术对人类大脑进行的研究已经产生了基于结构的 tau 蛋白病分类，这为更好地理解 tau 蛋白丝形成的重要性打开了大门。