University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.
Neurobiol Aging. 2012 May;33(5):1002.e17-27. doi: 10.1016/j.neurobiolaging.2011.09.012. Epub 2011 Oct 20.
Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages. It is therefore crucial to identify AD-like behavioral alterations which may reliably reflect the early stages of the pathology, thus permitting tests of more efficient early therapeutic interventions. Here, we demonstrated the very early expression of noncognitive AD-like symptoms, i.e., deficits in social interest, interaction and communication, in APP and APP-PS1 transgenic mice. Conversely, other noncognitive behaviors (sensori-motor gating) as well as cognitive abilities (spontaneous alternation) were unaltered in AD transgenics. Our data suggest that social deficits precede other neuropsychiatric and cognitive AD-like symptoms and can be employed as early markers of AD pathology in genetic mouse models.
模拟人类病理学的相关行为特征是包括阿尔茨海默病（AD）在内的神经退行性疾病动物模型的最重要挑战之一。事实上，携带淀粉样前体蛋白（APP）和早老素 1 基因（PS1）突变的最流行的遗传 AD 小鼠品系通常未能表现出明显的认知缺陷，或者仅在非常老年时才表现出缺陷。因此，确定类似于 AD 的行为改变非常重要，这可能可靠地反映病理学的早期阶段，从而允许对更有效的早期治疗干预措施进行测试。在这里，我们证明了 APP 和 APP-PS1 转基因小鼠中存在非认知性 AD 样症状（即社交兴趣、互动和交流缺陷）的早期表达。相反，AD 转基因小鼠的其他非认知行为（感觉运动门控）和认知能力（自发交替）没有改变。我们的数据表明，社交缺陷先于其他神经精神和认知 AD 样症状出现，可作为遗传小鼠模型中 AD 病理学的早期标志物。
