Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Psychiatry, Kinoko Espoir Hospital, Okayama, Japan.
Brain Pathol. 2020 Jul;30(4):811-830. doi: 10.1111/bpa.12843. Epub 2020 May 6.
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.
颗粒状/模糊星形胶质细胞（GFAs）是“与衰老相关的 tau 星形胶质病理”的一个亚型，在各种神经退行性疾病的病例中均有发现。然而，GFAs 的致病意义尚不清楚。我们通过免疫组织化学方法检查了 105 例病例的额皮质、尾状核、壳核和杏仁核，这些病例包括颗粒状银染病（AGD，N=26）、进行性核上性麻痹（PSP，N=10）、阿尔茨海默病（AD，N=20）和原发性年龄相关性 tau 病（PART，N=18），这些病例不含有 AGD，以及 31 例患有其他各种神经退行性疾病的病例，以明确：（i）AGD 和 PSP、AD 和 PART 中 GFAs 的分布模式；（ii）主要病理因素和年龄对 GFA 形成的影响；（iii）有助于理解 GFAs 形成过程的免疫组织化学特征。在 AGD 病例中，GFAs 始终出现在杏仁核（100%），其次是壳核（69.2%）和尾状核和额皮质（分别为 57.7%）。在无 AGD 的 PSP 病例中，GFAs 几乎一致地出现在所有检查区域（90-100%）。在无 AGD 的 AD 病例中，GFAs 的频率较低，主要出现在壳核（35.0%）和尾状核（30.0%）。无 AGD 的 PART 病例中 GFAs 最常见于杏仁核（35.3%），与 AD 病例相比，与 AGD 病例更相似。使用所有病例进行有序逻辑回归分析表明，额皮质和纹状体中 GFA 形成的最强独立因素是 PSP 的诊断，而杏仁核中的独立因素是 AGD。年龄与任何区域的 GFA 形成均无显著相关性。在 AGD 病例中，tau 的磷酸化和构象变化、与丛状星形胶质细胞不可区分的 Gallyas 阳性胶质丝以及自噬的激活依次发生。鉴于这些发现，AGD、PSP、AD 和 PART 病例可能表现出不同的 GFAs 分布，这可能为预测原发性 tau 病的潜在过程提供线索。
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