Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia
Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia
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DOI：
10.1111/bpa.12262
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发表时间：
2016-01-01
期刊：
影响因子：
6.4
通讯作者：
Takahashi, Hitoshi
中科院分区：
文献类型：
--
作者：
Takeuchi, Ryoko;Toyoshima, Yasuko;Takahashi, Hitoshi
肌萎缩侧索硬化症（ALS）可能伴有额颞叶痴呆（FTD）。我们报告一例神经胶质混合tau和TDP-43蛋白病在日本患者临床诊断为ALS-D。尸检显示下运动神经元丢失，脊髓和脑干锥体束变性。大脑表现出额颞叶变性（FTLD），中央前回中最严重的神经元丢失和神经胶质增生明显。虽然不太严重，但在其他大脑区域也观察到了这种变化，包括基底神经节和黑质。AT 8免疫染色显示，主要发生的星形胶质细胞tau病变称为球状星形胶质细胞包涵体（盖斯）是受影响的地区的一个特点。这些盖斯抗体都是阴性的。神经元和少突胶质细胞tau病变相对较少。pS409/410免疫染色也显示类似的神经元和神经胶质TDP-43病变。有趣的是，tau和TDP-43的偶尔共定位在盖斯中是明显的。免疫印迹分析显示了4-重复（4 R）tau蛋白病、皮质基底节变性和TDP-43蛋白病（ALS/FTLD-TDPTypeB）的特征性条带模式。在MAPT或TDP-43基因中未发现突变。我们认为该患者患有与运动神经元疾病和FTD相关的独特的散发性球状胶质混合4 R tau和TDP-43蛋白病。
Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDPTypeB. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.