摘要

       Braak 的嗜银颗粒 (ArGs) 是纺锤形的神经纤维结构，最初发现于患有成人痴呆症的患者中。我们最近观察到，在富含 ArG 的区域的大多数神经细胞中，tau 蛋白过度磷酸化，这表明这些颗粒可能是局部神经元中 tau 蛋白病理学的形态学表达。因此，本研究的目的是在三个使用 ArG 的情况下确定谷物是否与含有过度磷酸化 tau 的单个神经元相关。使用了加利亚斯银染色和 AT8 免疫细胞化学的组合。 AT8 是一种单克隆抗体，以磷酸化依赖性方式识别 tau。高达 80% 的 CA1 区锥体细胞显示其细胞体和树突的弥漫性 AT8 染色。大多数颗粒自由散布在整个神经纤维网中。然而，一些明显位于 AT8 免疫反应性锥体神经元顶端树突的侧枝中。树突分支通常形成灌木状分支，其中包含 ArG 簇。其他树突由单个树桩组成，其尖端包含一两个大颗粒。在 ArG 病例的高尔基考克斯制剂中也发现了树突分支的球状增大，其大小与 ArG 相对应，但在阿尔茨海默病病例或对照中没有。我们的结果表明，一些 ArG 在神经元的树突内形成，其最明显的病理是 tau 蛋白的弥漫性过度磷酸化。此外，含有晶粒的树突的形态表明，在带有 ArG 的神经元中正在发生树突逐渐收缩的过程。

       Braak's argyrophilic grains (ArGs) are spindle-shaped neuropil structures originally found in patients afflicted with adult onset dementia. We recently observed that tau protein is hyperphosphorylated in most nerve cells in areas rich in ArGs, suggesting that these grains may be a morphological expression of tau protein pathology in local neurons. The aim of this study was therefore to determine in three cases with ArGs whether grains are associated with individual neurons containing hyperphosphorylated tau. A combination of Gallyas silver staining and AT8 immunocytochemistry was used. AT8 is a monoclonal antibody that recognizes tau in a phosphorylation-dependent manner. Up to 80% of pyramidal cells of sector CA1 showed diffuse AT8 staining of their cell bodies and dendrites. Most grains were freely scattered throughout the neuropil. However, some were clearly located in side-branches of apical dendrites of AT8 immunoreactive pyramidal neurons. Dendritic branches often formed bush-like ramifications containing clusters of ArGs. Other dendrites consisted of a single stump containing one or two large grains at their tips. Spheroidal enlargements of dendritic branches, with a size corresponding to ArGs, were also found in Golgi Cox preparations of cases with ArGs but not in Alzheimer's disease cases or in controls. Our results show that some ArGs are formed within dendrites of neurons whose most obvious pathology is a diffuse hyperphosphorylation of the tau protein. Furthermore, morphology of dendrites containing grains suggests that a process of progressive shrinkage of dendrites is taking place in neurons bearing ArGs.

https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2990.1998.00090.x