Department of Pathology, University Clinical Centre Maribor, Maribor, Slovenia.
Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Neuropathol Appl Neurobiol. 2018 Oct;44(6):550-562. doi: 10.1111/nan.12456. Epub 2018 Jan 7.
This report presents the clinical course, neuropathology and ultrastructure of neuronal tau inclusions of four Slovene relatives with P364S MAPT mutation.
The clinical history of three out of four P364S MAPT mutation carriers was taken. After formalin fixation, thorough sampling of the central nervous system was followed by paraffin embedding, H&E, Gallyas, Bielschowsky and immunostaining with AT8, anti-3R, anti-4R tau, anti-amyloid-β, anti-TDP43 and anti-alpha-synuclein antibodies. The distribution and density of different types of neuronal tau inclusions were semiquantitatively assessed. In addition, the ultrastructure of neuronal tau inclusions was analysed.
Macroscopic examination of the brains was unremarkable. Microscopically, neuronal tau inclusions of almost all known types were widespread and distributed fairly uniformly in all cases. Pick bodies and swollen neurones were found in only one family member. Mutant tau was composed of 3R and 4R isoforms, with a slight predominance of 3R tau. Composite neuronal tau inclusion (CNTI), found in all four relatives, was a hallmark of the P364S MAPT mutation. CNTI showed compartmental differences in H&E and Gallyas staining, tau isoforms immunolabelling and ultrastructure, displaying fuzzy fibrils in the core and paired twisted tubules at the periphery.
P364S MAPT mutation is characterized clinically by a variable combination of frontotemporal dementia, parkinsonism and motor neurone disease of short duration, and neuropathologically by a widespread uniform distribution of all known neuronal tau inclusions in one family member. Two-compartment CNTI is a unique characteristic of the P364S MAPT mutation.
本报告介绍了 4 名斯洛文尼亚 P364S MAPT 突变携带者的临床病程、神经病理学和神经元 tau 包涵体的超微结构。
我们记录了其中 3 名 P364S MAPT 突变携带者的临床病史。福尔马林固定后，对中枢神经系统进行了彻底取样，然后进行石蜡包埋、H&E、Gallyas、Bielschowsky 染色以及 AT8、抗 3R、抗 4R tau、抗淀粉样β、抗 TDP43 和抗α-突触核蛋白抗体的免疫染色。对不同类型的神经元 tau 包涵体的分布和密度进行了半定量评估。此外，还分析了神经元 tau 包涵体的超微结构。
大脑的大体检查未见明显异常。显微镜下，几乎所有已知类型的神经元 tau 包涵体在所有病例中均广泛分布且分布均匀。仅在 1 名家族成员中发现 Pick 体和肿胀神经元。突变 tau 由 3R 和 4R 异构体组成，3R tau 略有优势。在所有 4 名亲属中均发现的复合神经元 tau 包涵体（CNTI）是 P364S MAPT 突变的标志。CNTI 在 H&E 和 Gallyas 染色、tau 异构体免疫标记和超微结构方面存在区室差异，在核心显示出模糊纤维，在外周显示出成对扭曲的小管。
P364S MAPT 突变的临床特征为额颞叶痴呆、帕金森病和运动神经元病的长短不一的组合，神经病理学特征为一名家族成员中所有已知神经元 tau 包涵体的广泛均匀分布。双区 CNTI 是 P364S MAPT 突变的独特特征。
