Astrocytes expressing hyperphosphorylated tau protein without glial fibrillary tangles in argyrophilic grain disease
Astrocytes expressing hyperphosphorylated tau protein without glial fibrillary tangles in argyrophilic grain disease
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DOI：
10.1007/s004010051077
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发表时间：
1999-09-01
影响因子：
12.7
通讯作者：
Tolnay, M
中科院分区：
文献类型：
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作者：
Botez, G;Probst, A;Tolnay, M
嗜银颗粒病(AGD)是一种常见的迟发性痴呆，其特征是在海马体、内嗅皮层、杏仁核和下丘脑出现Galyas染色的神经纤维颗粒。在富含嗜银颗粒(ARGs)的区域，可以看到大量含有过度磷酸化的tau蛋白但没有缠结的神经元。第三种类型的改变包括白质少突胶质细胞中细长的嗜银和tau免疫反应阳性的细胞质内含物，即卷曲小体。我们现在扩展早期对AGO(20例)神经胶质病理的研究，并将结果与老年(10例)和阿尔茨海默病(AD；7例)的神经胶质变化进行比较。在20例AGO患者中，杏仁核和前内嗅皮质均可见大量非嗜银、非神经元tau阳性的星形细胞，而AD患者中未见。用磷酸化依赖的抗tau抗体AT8、抗胶质纤维酸性蛋白和抗CD44对石蜡切片进行双标记实验，发现这些标记在星状细胞中共表达。CD44的高表达提示它们可能与反应性星形胶质细胞相对应。与皮质基底性变性(CBD)中的星形细胞斑块不同，AT8活性在星形细胞突起的远端积聚，而AGO中的tau活性在所有星形细胞区都被发现。胶质纤维缠结的缺失进一步区分了AGO中tau标记的星形胶质细胞与CUD中的星形胶质细胞斑块和进行性核上性麻痹(PSP)中的簇状星形胶质细胞。与阿尔茨海默病和老年非痴呆对照组相比，tau阳性的非嗜银星形胶质细胞在AGO的前缘结构中的发现是一致的。我们的发现表明，AGO中神经胶质细胞群的病理分布比之前想象的更广泛，这将有助于进一步帮助AGO与其他神经退行性疾病，包括AD、PSP、CBD和Pick病进行鉴别。
Argyrophilic grain disease (AgD), a frequent type of late onset dementia, is characterized by the occurrence of Gallyas-stained neuropil grains in the hippocampus, entorhinal cortex, amygdala and hypothalamus. High numbers of neurons containing hyperphosphorylated tau protein, but devoid of tangles, are encountered in areas rich in argyrophilic grains (ArGs). A third type of change consists of slender argyrophilic and tau-immunoreactive cytoplasmic inclusions in white matter oligodendrocytes, the coiled bodies. We now extend earlier studies on glial pathology in Ago (20 cases) and compare the results with glial changes in old age (10 cases) and Alzheimer's disease (AD; 7 cases). Numerous non-argyrophilic, non-neuronal tau-positive stellate cells in the amygdala and anterior entorhinal cortex were consistently found in all of the 20 Ago cases but not in AD cases. Double-labelling experiments performed on paraffin sections with phosphorylation-dependent anti-tau antibody AT8, anti-glial fibrillary acidic protein and anti-CD44, revealed coexpression of these markers in stellate cells. The high expression of CD44 indicate that they probably correspond to reactive astrocytes. Unlike astrocytic plaques in corticobasal degeneration (CBD), where AT8 reactivity is accumulating in distal astrocytic processes, tau reactivity in Ago was found in all astrocytic cell compartments. The absence of glial fibrillary tangles further distinguished tau-labelled astrocytes in Ago from astrocytic plaques in CUD and tufted astrocytes in progressive supranuclear palsy (PSP). In contrast to AD and aged non-demented control cases tau-positive non-argyrophilic astrocytes represent a consistent finding in anterior limbic structures in Ago. Our findings point to a more widespread pathology of the glial cell population in Ago than previously supposed, and will be of further help in differentiating Ago from other neurodegenerative disorders, including AD, PSP, CBD and Pick's disease.