Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala, hippocampus, dentate gyrus, presubiculum, subiculum, hypothalamic nuclei, temporal cortex, and neocortex and brainstem, thus suggesting that argyrophilic grain pathology is a natural model of tau propagation. One series of WT mice was unilaterally inoculated in the hippocampus with sarkosyl-insoluble and sarkosyl-soluble fractions from “pure” AGD at the age of 3 or 7/12 months and killed 3 or 7 months later. Abnormal hyper-phosphorylated tau deposits were found in ipsilateral hippocampal neurons, grains (dots) in the hippocampus, and threads, dots and coiled bodies in the fimbria, as well as the ipsilateral and contralateral corpus callosum. The extension of lesions was wider in animals surviving 7 months compared with those surviving 3 months. Astrocytic inclusions were not observed at any time. Tau deposits were mainly composed of 4Rtau, but also 3Rtau. For comparative purposes, another series of WT mice was inoculated with sarkosyl-insoluble fractions from primary age-related tauopathy (PART), a pure neuronal neurofibrillary tangle 3Rtau + 4Rtau tauopathy involving the deep temporal cortex and limbic system. Abnormal hyper-phosphorylated tau deposits were found in neurons in the ipsilateral hippocampus, coiled bodies and threads in the fimbria, and the ipsilateral and contralateral corpus callosum, which extended with time along the anterior-posterior axis and distant regions such as hypothalamic nuclei and nuclei of the septum when comparing mice surviving 7 months with mice surviving 3 months. Astrocytic inclusions were not observed. Tau deposits were mainly composed of 4Rtau and 3Rtau. These results show the capacity for seeding and spreading of AGD tau and PART tau in the brain of WT mouse, and suggest that characteristics of host tau, in addition to those of inoculated tau, are key to identifying commonalities and differences between human tauopathies and corresponding murine models.

嗜银粒病 (AGD) 是一种常见的 4R-tau 蛋白病，可导致或促成老年人的认知障碍。AGD 的神经病理学特征是神经元中的预缠结、称为颗粒、线、刺状星形胶质细胞的树突状肿胀以及边缘系统中少突胶质细胞中的卷曲体。AGD 具有逐渐累及内嗅皮层、杏仁核、海马、齿状回、前托、下托、下丘脑核、颞叶皮层、新皮层和脑干的特征模式，因此表明嗜银颗粒病理学是 tau 传播的自然模型。一组 WT 小鼠在 3 或 7/12 个月大时在海马体中单侧接种来自“纯”AGD 的肌氨酰不溶性和肌氨酰可溶性部分，并在 3 或 7 个月后处死。在同侧海马神经元、海马中的颗粒（点）和菌毛中的线、点和盘绕体以及同侧和对侧胼胝体中发现异常的高磷酸化tau蛋白沉积物。与存活 3 个月的动物相比，存活 7 个月的动物的病变范围更广。在任何时候都没有观察到星形细胞内含物。Tau 矿床主要由 4Rtau 和 3Rtau 组成。出于比较目的，另一系列 WT 小鼠接种了来自原发性年龄相关性 tauopathy (PART) 的 sarkosyl 不溶性部分，这是一种涉及深部颞叶皮层和边缘系统的纯神经元神经原纤维缠结 3Rtau + 4Rtau tauopathy。在同侧海马的神经元、卷曲体和伞毛的线中发现异常的高磷酸化 tau 沉积物，与存活 7 个月的小鼠和存活 3 个月的小鼠相比，同侧和对侧胼胝体沿前后轴和远处区域（如下丘脑核和中隔核）随时间延长。未观察到星形胶质细胞内含物。Tau 矿床主要由 4Rtau 和 3Rtau 组成。这些结果显示了 AGD tau 和 PART tau 在 WT 小鼠大脑中的播种和传播能力，并表明宿主 tau 的特征以及接种 tau 的特征是识别人类 tau 病和相应的 tau 病之间的共性和差异的关键。鼠模型。当比较存活 7 个月的小鼠和存活 3 个月的小鼠时，它会随着时间沿前后轴和远处区域（例如下丘脑核和隔膜的核）而延长。未观察到星形胶质细胞内含物。Tau 矿床主要由 4Rtau 和 3Rtau 组成。这些结果显示了 AGD tau 和 PART tau 在 WT 小鼠大脑中的播种和传播能力，并表明宿主 tau 的特征以及接种的 tau 的特征是识别人类 tau 病和相应的 tau 病之间的共性和差异的关键鼠模型。当比较存活 7 个月的小鼠和存活 3 个月的小鼠时，它会随着时间沿前后轴和远处区域（例如下丘脑核和隔膜的核）而延长。未观察到星形胶质细胞内含物。Tau 矿床主要由 4Rtau 和 3Rtau 组成。这些结果显示了 AGD tau 和 PART tau 在 WT 小鼠大脑中的播种和传播能力，并表明宿主 tau 的特征以及接种的 tau 的特征是识别人类 tau 病和相应的 tau 病之间的共性和差异的关键鼠模型。