Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Medical Interactive Research and Academia Industry Collaboration Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Int J Mol Sci. 2021 May 24;22(11):5549. doi: 10.3390/ijms22115549.
Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.
阿尔茨海默病(AD)是一种与年龄相关的进行性神经退行性疾病。人们普遍认为,AD 主要是由细胞外淀粉样β(Aβ)的积累和细胞内神经原纤维缠结引起的。Aβ在认知障碍出现前多年就开始积累,这表明如果在 AD 的早期阶段开始干预,目前可用的干预措施的效果会更好。为了了解 AD 发病机制,已经开发了各种具有加速 Aβ和 tau 缠结积累的转基因小鼠模型。然而,这些模型都没有表现出人类 AD 中存在的所有病理学。为了克服这些不理想的表型,开发了具有基于触摸屏任务的基因敲入小鼠,以更好地评估候选治疗药物在 AD 早期模型中的疗效。本综述从生物标志物和认知障碍的角度评估了几种 AD 小鼠模型,并讨论了它们作为提供新型 AD 治疗方法的工具的潜力。