Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Acta Neuropathol. 2023 Aug;146(2):211-226. doi: 10.1007/s00401-023-02598-6. Epub 2023 Jun 23.
Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease.
两名 MAPT ∆K281 缺失突变的兄弟姐妹均患有额颞叶痴呆。尸检时，新皮质和一些皮质下区域（包括海马、尾状核/壳核和苍白球）的神经元和神经胶质细胞中存在大量过度磷酸化的 3R Tau 包涵体。这些包涵体对 Bodian 银呈嗜银性，但对 Gallyas-Braak 银呈阴性。它们不被针对 S262 和/或 S356 磷酸化的 tau 的抗体标记。这些包涵体被发光共轭寡噻吩 HS-84 染色，但不被 bTVBT4 染色。电镜 cryo-microscopy 显示 tau 丝的核心由 3R Tau 的 K254-F378 残基组成，与 Pick 病的核心无区别。我们的结论是，MAPT 突变 ∆K281 导致 Pick 病。
