Howlett D R, Richardson J C
Neurology CEDD, GlaxoSmithKline, Harlow, Essex, UK.
Histol Histopathol. 2009 Jan;24(1):83-100. doi: 10.14670/HH-24.83.
Alzheimer's disease (AD) is characterized by a number of pathological features, notably extracellular senile plaques composed of the beta-amyloid protein (Abeta) and neurofibrillary tangles (NFT's), which are intracellular inclusions of hyperphosphorylated tau protein. In their attempts to generate a model of AD, many laboratories have produced transgenic mice that overexpress the amyloid precursor protein (APP), in particular, mutant APP which is associated with familial forms of AD in man. Histopathological assessment shows that APP transgenic mice demonstrate an accumulation of Abeta in plaques from an early age; these plaques are invariably surrounded by activated inflammatory cells such as astrocytes and microglia, as is common in AD brain. Also, commonly associated with the plaques is hyperphosphorylated tau, although this does not take on the NFT phenotype observed in AD. Atrophy and neurodegenerative pathology are other common features of AD; some neuronal loss is evident in close proximity to plaques in APP transgenic mice although this is not extensive. Consequently, it is evident that APP transgenic mice exhibit, to some degree, many of the pathological features of AD.
阿尔茨海默病（AD）具有多种病理特征，尤其是由β-淀粉样蛋白（Aβ）组成的细胞外老年斑和神经原纤维缠结（NFTs），后者是细胞内过度磷酸化的tau蛋白内含物。在试图构建AD模型的过程中，许多实验室培育出了过度表达淀粉样前体蛋白（APP）的转基因小鼠，特别是与人类家族性AD形式相关的突变型APP。组织病理学评估显示，APP转基因小鼠从小就表现出Aβ在斑块中的积累；这些斑块总是被诸如星形胶质细胞和小胶质细胞等活化的炎症细胞所包围，这在AD大脑中很常见。此外，与斑块通常相关的还有过度磷酸化的tau，尽管它并未呈现出AD中观察到的NFT表型。萎缩和神经退行性病理是AD的其他常见特征；在APP转基因小鼠中，靠近斑块处有一些神经元丢失明显，尽管并不广泛。因此，很明显APP转基因小鼠在某种程度上表现出了AD的许多病理特征。
