Zhang Lu, Toyoshima Yasuko, Takeshima Akari, Shimizu Hiroshi, Tomita Itsuro, Onodera Osamu, Takahashi Hitoshi, Kakita Akiyoshi
Departments of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
Department of Neurology, Nagasaki-kita Hospital, Nagasaki, Japan.
Neuropathology. 2021 Jun;41(3):174-182. doi: 10.1111/neup.12707. Epub 2020 Nov 17.
Progressive supranuclear palsy (PSP) presents with a wide variety of signs/symptoms, making early initial diagnosis difficult. We investigated the clinical and neuropathological features of five patients with autopsy-proven PSP of short duration, ranging from 11 to 41 months (average, 26.2 months) due to unexpected death, focusing particularly on the distribution and severity of neuronal loss as well as neuronal and glial tau pathology in the affected brain. Clinical features were studied retrospectively through careful review of the medical records, and neuropathological examinations were carried out, along with tau immunohistochemistry using a monoclonal antibody AT8. These patients were diagnosed as having probable PSP (n = 4) and suggestive PSP (n = 1), respectively. In all cases, neuronal loss was evident in the substantia nigra, subthalamic nucleus, globus pallidus, and locus ceruleus. AT8-identified tau lesions, that is, pretangles/neurofibrillary tangles (PTs/NFTs), tufted astrocytes (TAs), and coiled bodies/neuropil threads (CBs/NTs), were distributed widely in the brain regions, especially in patients with longer disease duration. All cases showed variation in the regional tau burden among PTs/NFTs, TAs, and CBs/NTs. There was also a tendency for tau deposition to be more predominant in neuronal cells in the brainstem and cerebellum and in glial cells in the cerebral cortex and subcortical gray matter. These findings suggest that in PSP, the initial signs/symptoms are associated with degeneration and subsequent death of neurons with pathological tau deposition, and that the tau deposition in neuronal cells is independent of that in glial cells.
进行性核上性麻痹（PSP）表现出多种多样的体征/症状，使得早期初步诊断困难。我们调查了5例经尸检证实病程较短（11至41个月，平均26.2个月）的PSP患者的临床和神经病理学特征，这些患者因意外死亡，特别关注受影响大脑中神经元丢失的分布和严重程度以及神经元和胶质细胞的tau病理变化。通过仔细查阅病历对临床特征进行回顾性研究，并进行神经病理学检查，同时使用单克隆抗体AT8进行tau免疫组织化学检测。这些患者分别被诊断为可能的PSP（n = 4）和疑似PSP（n = 1）。在所有病例中，黑质、丘脑底核、苍白球和蓝斑均有明显的神经元丢失。AT8识别的tau病变，即前缠结/神经原纤维缠结（PTs/NFTs）、簇状星形胶质细胞（TAs）和螺旋体/神经毡丝（CBs/NTs），广泛分布于脑区，尤其是病程较长的患者。所有病例在PTs/NFTs、TAs和CBs/NTs之间的区域tau负荷均存在差异。tau沉积在脑干和小脑的神经元细胞以及大脑皮质和皮质下灰质的胶质细胞中也更倾向于占主导地位。这些发现表明，在PSP中，最初的体征/症状与伴有病理性tau沉积的神经元变性及随后的死亡有关，并且神经元细胞中的tau沉积与胶质细胞中的tau沉积无关。
