Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Neurobiol Aging. 2013 May;34(5):1328-42. doi: 10.1016/j.neurobiolaging.2012.11.008. Epub 2012 Dec 12.
Using microarray technology we studied the genome-wide gene expression profiles in the frontal cortex of APPswe/PS1dE9 mice and age and sex-matched littermates at the age of 2, 3, 6, 9, 12, and 15-18 months to investigate transcriptional changes that are associated with beta amyloid protein (Aβ) plaque formation and buildup. We observed the occurrence of an immune response with glial activation, but no changes in genes involved in synaptic transmission or plasticity. Comparison of the mouse gene expression data set with a human data set representing the course of Alzheimer's disease revealed a strikingly limited overlap between gene expression in the APPswe/PS1dE9 and human Alzheimer's disease prefrontal cortex. Only plexin domain containing 2, complement component 4b, and solute carrier family 14 (urea transporter) member 1 were significantly upregulated in the mouse and human brain which might suggest a function in Aβ pathology for these 3 genes. In both data sets we detected clusters of upregulated genes involved in immune-related processes. We conclude that the APPswe/PS1dE9 mouse can be a good model to study the immune response associated with cortical Aβ plaques.
我们使用微阵列技术研究了 APPswe/PS1dE9 小鼠和年龄及性别匹配的同窝对照在 2、3、6、9、12 和 15-18 个月时额皮质的全基因组基因表达谱，以研究与β淀粉样蛋白（Aβ）斑块形成和积累相关的转录变化。我们观察到伴有神经胶质激活的免疫反应发生，但涉及突触传递或可塑性的基因没有变化。将小鼠基因表达数据集与代表阿尔茨海默病病程的人类数据集进行比较，发现 APPswe/PS1dE9 小鼠和人类阿尔茨海默病前额叶皮质中的基因表达之间的重叠非常有限。只有神经丛蛋白 2、补体成分 4b 和溶质载体家族 14（尿素转运体）成员 1 在小鼠和人大脑中显著上调，这可能表明这 3 个基因在 Aβ 病理学中具有功能。在这两个数据集我们都检测到与免疫相关过程上调基因的聚类。我们得出结论，APPswe/PS1dE9 小鼠可以成为研究与皮质 Aβ斑块相关的免疫反应的良好模型。
