School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.
Med Res Rev. 2020 Jan;40(1):431-458. doi: 10.1002/med.21624. Epub 2019 Jul 22.
Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti-AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti-AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti-AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti-AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti-AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.
阿尔茨海默病（AD）是最常见的痴呆症形式，是一种进行性神经退行性疾病。在过去的几十年中，大量有前途的药物候选物在临床前研究中显示出显著的抗 AD 作用，但在临床试验中失败。其中一个主要原因可能是缺乏合适的动物模型来评估抗 AD 药物。超过 95%的 AD 病例为散发性 AD（sAD）。然而，抗 AD 药物候选物主要在家族性 AD（fAD）动物模型中进行测试。sAD 和 fAD 之间的差异可能导致抗 AD 药物开发过程中的高失败率。因此，迫切需要开发抗 AD 药物的理想 sAD 动物模型。在这里，我们总结了现有的 sAD 动物模型，包括它们的方法学、病理特征和潜在的机制。还讨论了这些 sAD 动物模型的局限性和该领域的未来趋势。
