Kubota Manabu, Endo Hironobu, Takahata Keisuke, Tagai Kenji, Suzuki Hisaomi, Onaya Mitsumoto, Sano Yasunori, Yamamoto Yasuharu, Kurose Shin, Matsuoka Kiwamu, Seki Chie, Shinotoh Hitoshi, Kawamura Kazunori, Zhang Ming-Rong, Takado Yuhei, Shimada Hitoshi, Higuchi Makoto
Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
Department of Psychiatry, Kyoto University Graduate School of Medicine, Sakyo-ku Kyoto 606-8507, Japan.
Brain Commun. 2024 Mar 1;6(2):fcae075. doi: 10.1093/braincomms/fcae075. eCollection 2024.
Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. neuropathological assessments of frontotemporal dementia at an individual level have hitherto not been successful. In this study, we aim to classify patients with frontotemporal dementia based on topologies of tau protein aggregates captured by PET with F-florzolotau (aka F-APN-1607 and F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer's disease as well as in non-Alzheimer's disease tauopathies. Twenty-six patients with frontotemporal dementia, 15 with behavioural variant frontotemporal dementia and 11 with other frontotemporal dementia phenotypes, and 20 age- and sex-matched healthy controls were included in this study. They underwent PET imaging of amyloid and tau depositions with C-PiB and F-florzolotau, respectively. By combining visual and quantitative analyses of PET images, the patients with behavioural variant frontotemporal dementia were classified into the following subgroups: (i) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three-repeat tauopathies ( = 3), (ii) predominant tau accumulations in posterior cortical and subcortical structures indicative of four-repeat tauopathies ( = 4); (iii) amyloid and tau accumulations consistent with Alzheimer's disease ( = 4); and (iv) no overt amyloid and tau pathologies ( = 4). Despite these distinctions, clinical symptoms and localizations of brain atrophy did not significantly differ among the identified behavioural variant frontotemporal dementia subgroups. The patients with other frontotemporal dementia phenotypes were also classified into similar subgroups. The results suggest that PET with F-florzolotau potentially allows the classification of each individual with frontotemporal dementia on a neuropathological basis, which might not be possible by symptomatic and volumetric assessments.
额颞叶痴呆是指一组具有多样临床和神经病理学特征的神经退行性疾病。迄今为止，对额颞叶痴呆进行个体水平的神经病理学评估尚未成功。在本研究中，我们旨在基于用F-氟罗佐洛 tau（又名F-APN-1607和F-PM-PBB3）进行PET捕获的tau蛋白聚集体拓扑结构对额颞叶痴呆患者进行分类，这使得在阿尔茨海默病以及非阿尔茨海默病tau蛋白病中对不同的tau原纤维进行高对比度成像成为可能。本研究纳入了26例额颞叶痴呆患者，其中15例为行为变异型额颞叶痴呆，11例为其他额颞叶痴呆表型，以及20名年龄和性别匹配的健康对照。他们分别接受了用C-PiB和F-氟罗佐洛tau对淀粉样蛋白和tau沉积进行的PET成像。通过结合PET图像的视觉和定量分析，行为变异型额颞叶痴呆患者被分为以下亚组：（i）额颞叶和额边缘叶皮质中主要的tau积聚，类似于三重重复tau蛋白病（n = 3）；（ii）后皮质和皮质下结构中主要的tau积聚，提示四重重复tau蛋白病（n = 4）；（iii）与阿尔茨海默病一致的淀粉样蛋白和tau积聚（n = 4）；以及（iv）无明显的淀粉样蛋白和tau病理学改变（n = 4）。尽管存在这些差异，但在已识别的行为变异型额颞叶痴呆亚组中，临床症状和脑萎缩部位并无显著差异。其他额颞叶痴呆表型的患者也被分为类似的亚组。结果表明，用F-氟罗佐洛tau进行PET有可能在神经病理学基础上对每例额颞叶痴呆患者进行分类，而这通过症状和体积评估可能无法实现。
