Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies.

中文翻译：

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与神经退行性疾病中粒状/模糊星形胶质细胞的发育和分布有关的因素。

患有各种神经退行性疾病的病例中注意到了颗粒/模糊星形胶质细胞（GFA），它是“与衰老有关的tau型星形胶质细胞病变”的一种亚型。但是，GFA的致病意义尚不清楚。我们用免疫组织化学方法检查了105例由嗜银粒病（AGD，N = 26）和进行性核上性麻痹（PSP，N = 10），阿尔茨海默氏病（AD，N = 20）组成的额叶皮层，尾状核，壳状核和杏仁核）和缺乏AGD的原发性年龄相关性tauopathy病例（PART，N = 18），以及31例患有其他神经退行性疾病的病例，以阐明（i）AGD中GFA的分布模式，以及缺乏AGD的PSP，AD和PART， （ii）主要病理因素和年龄对GFA形成的影响，以及（iii）有助于了解GFA形成过程的免疫组织化学特征。在AGD情况下，GFA持续发生在杏仁核（100％）中，其次是壳核（69.2％），尾状核和额叶皮层（分别为57.7％）。在没有AGD的PSP病例中，在所有检查的区域（90-100％）几乎一致地注意到了GFA。在没有AGD的AD病例中，GFA的频率较低，优选在壳核（35.0％）和尾状核（30.0％）中发育。没有AGD的PART病例在杏仁核中的GFA频率最高（35.3％），与AGD相比，与AD病例更为相似。所有病例的有序逻辑回归分析表明，额叶皮层和纹状体中GFA形成的最强独立因素是PSP的诊断，而杏仁核中AGD的诊断是最重要的。在任何地区，年龄与总建筑面积的形成没有显着相关。在AGD病例的GFA中，tau的磷酸化和构象变化 Gallyas阳性神经胶质线与簇状星形胶质细胞的神经胶质线无法区分，并且自噬的激活顺序发生。鉴于这些发现，AGD，PSP，AD和PART病例可能显示GFA的不同分布，这可能为预测原发性疾病的潜在过程提供线索。