MRC Laboratory of Molecular Biology, Cambridge, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Adv Exp Med Biol. 2021;1281:177-199. doi: 10.1007/978-3-030-51140-1_12.
Filamentous inclusions of tau protein are found in cases of inherited and sporadic frontotemporal dementias (FTDs). Mutations in MAPT, the tau gene, cause approximately 5% of cases of FTD. They proved that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Clinically and pathologically, cases with MAPT mutations can resemble sporadic diseases, such as Pick's disease, globular glial tauopathy, progressive supranuclear palsy and corticobasal degeneration. The structures of tau filaments from Pick's disease and corticobasal degeneration, determined by electron cryo-microscopy, revealed the presence of specific tau folds in each disease, with no inter-individual variation. The same was true of chronic traumatic encephalopathy.
tau 蛋白丝包涵体可见于遗传性和散发性额颞叶痴呆(FTD)病例中。MAPT,即 tau 基因的突变约占 FTD 的 5%。这些研究证明 tau 蛋白功能障碍足以导致神经退行性变和痴呆。临床上和病理学上,携带 MAPT 突变的病例类似于散发性疾病,如 Pick 病、球状神经胶质 tau 病、进行性核上性麻痹和皮质基底节变性。通过电子冷冻显微镜确定的 Pick 病和皮质基底节变性 tau 丝的结构显示,每种疾病中都存在特定的 tau 折叠,而且个体之间没有差异。慢性创伤性脑病也是如此。