VIB Center for Brain and Disease Research, Leuven, Belgium.
KU Leuven Department for Neurosciences, KU Leuven, Leuven, Belgium.
J Alzheimers Dis. 2018;66(2):801-809. doi: 10.3233/JAD-180410.
Commonly used Alzheimer's disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old AppNL/NL mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits.
常用的阿尔茨海默病小鼠模型基于人淀粉样前体蛋白（APP）基因的异位过表达，以及突变早老素基因。令人惊讶的是，携带单一 APP 瑞典突变（AppNL）的人源化 APP 基因敲入小鼠模型未能发展出淀粉样斑块聚集或认知缺陷。在这里，我们在更老年时对该突变的影响进行了特征描述。我们表明，24 月龄的 AppNL/NL 小鼠，尽管在额皮质中出现了与年龄相关的可溶性淀粉样β寡聚物的增加，但它们不会发展出淀粉样斑块沉积、反应性神经胶质增生或认知缺陷。
