神经突斑促进阿尔茨海默病小鼠模型中 tau 的病理性转化。

The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model.

机构信息

Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.

Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

出版信息

Nat Commun. 2016 Jul 4;7:12082. doi: 10.1038/ncomms12082.

A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau.

阿尔茨海默病（AD）中的一个核心问题是神经突斑块是否足以导致 tau 病理学的发展。在 AD 小鼠模型中，β-淀粉样蛋白沉积物周围的神经突中发现 tau 过度磷酸化，但不存在 tau 的病理性转化。同样，在小鼠中表达人类 tau 重复结构域不足以驱动 tau 的病理性转化。在这里，我们开发了一种表达人类 tau 重复结构域的 Aβ-淀粉样变性小鼠模型，并表明在这些小鼠中，神经突斑块促进了野生型 tau 的病理性转化。我们表明，tau 片段促使依赖于神经突斑块的野生型 tau 的病理性转化，该转化从大脑皮层和海马体扩散到脑干。这些结果表明，除了神经突斑块之外，还需要第二个决定因素来驱动野生型 tau 的转化。