Ferrer I, Hernández I, Boada M, Llorente A, Rey M J, Cardozo A, Ezquerra M, Puig B
Banc de Teixits Neurològics, Universitat de Barcelona/Hospital Clinic, Barcelona, Spain.
Acta Neuropathol. 2003 Nov;106(5):419-35. doi: 10.1007/s00401-003-0756-4. Epub 2003 Aug 29.
The clinical, neuroradiological, neuropathological and biochemical findings in four patients with primary progressive aphasia and tauopathy are described. The aphasic syndrome preceded by several years the appearance of other symptoms in every case. Asymmetrical apraxia with alien hand phenomenon occurred in one case. Frontotemporal symptoms occurred in three cases, but progressed to dramatic cognitive devastation in only one of these. Generalized dementia consistent with probable Alzheimer's disease (AD) developed with time in another. Cerebral computer tomography scans, magnetic resonance imaging and SPECT studies revealed marked asymmetries in one case, and showed nonspecific cerebral atrophy in the remaining ones. The neuropathological examination revealed typical corticobasal degeneration (CBD) in one case; CBD and AD in another; and atypical CBD, argyrophilic grain disease (AGD) and alpha-synucleinopathy consistent with Parkinson's disease in a third. Unique neuropathological findings were found in the remaining case. This was characterized by severe cerebral atrophy, marked neuronal loss in the cerebral cortex and abnormal tau deposition in neurons of the cerebral cortex, diencephalon and brain stem. Ballooned neurons, Pick bodies, generalized cortical neurofibrillary tangles and astrocytic plaques were absent. However, massive globular inclusions, containing phospho-tau, occurred in glial cells, mainly oligodendrocytes, in the white matter. Biochemical studies of frontal homogenates revealed four bands of 73/74, 68, 64 and 60 kDa of phosphorylated tau (using antibodies recognizing phospho-tau Thr181, Ser262 and Ser422) in the patient with AD and CBD, suggesting a predominant AD pattern in this case. Two bands of 68 and 64 kDa of phospho-tau were recovered in the sarkosyl-insoluble fraction in the other three cases. This pattern is similar to that found in CBD, progressive supranuclear palsy and AGD. Taken together, the present series further supports pure and combined CBD as causes of primary progressive aphasia, and they extend the hypothesis that primary progressive aphasia may be the initial symptom of distinct tauopathies.
本文描述了4例原发性进行性失语伴tau蛋白病患者的临床、神经放射学、神经病理学和生化检查结果。在每例患者中，失语综合征均先于其他症状出现数年。1例患者出现不对称失用症伴异己手现象。3例患者出现额颞叶症状，但仅1例进展为严重认知功能障碍。另1例患者随时间推移发展为符合可能的阿尔茨海默病（AD）的广泛性痴呆。脑计算机断层扫描、磁共振成像和单光子发射计算机断层扫描研究显示，1例患者存在明显不对称性，其余患者表现为非特异性脑萎缩。神经病理学检查发现，1例患者为典型的皮质基底节变性（CBD）；另1例为CBD和AD；第3例为非典型CBD、嗜银颗粒病（AGD）和符合帕金森病的α-突触核蛋白病。其余1例患者有独特的神经病理学发现。其特征为严重脑萎缩、大脑皮质明显神经元丢失以及大脑皮质、间脑和脑干神经元中异常tau蛋白沉积。未见气球样神经元、Pick小体、广泛性皮质神经原纤维缠结和星形细胞斑。然而，白质中的胶质细胞（主要是少突胶质细胞）中出现了大量含磷酸化tau蛋白（phospho-tau）的球形包涵体。额叶匀浆的生化研究显示，AD和CBD患者的额叶匀浆中出现了4条磷酸化tau蛋白条带，分子量分别为73/74、68、64和60 kDa（使用识别磷酸化tau蛋白Thr181、Ser262和Ser422的抗体），提示该病例以AD模式为主。其他3例患者的 Sarkosyl不溶性部分中回收了2条磷酸化tau蛋白条带，分子量分别为68和64 kDa。这种模式与CBD、进行性核上性麻痹和AGD中发现的模式相似。综上所述，本系列研究进一步支持单纯性和合并性CBD是原发性进行性失语的病因，并扩展了原发性进行性失语可能是不同tau蛋白病初始症状的假说。
