阿尔茨海默病动物模型:当前策略与新方向。
Animal models of Alzheimer's disease: Current strategies and new directions.
机构信息
Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. E-mail:
出版信息
Zool Res. 2024 Nov 18;45(6):1385-1407. doi: 10.24272/j.issn.2095-8137.2024.274.
Animal models constructed using pathogenic factors have significantly advanced drug development for Alzheimer's disease (AD). These predominantly transgenic models, mainly in mice, replicate pathological phenotypes through gene mutations associated with familial AD cases, thus serving as vital tools for assessing drug efficacy and for performing mechanistic studies. However, the species-specific differences and complex, heterogeneous nature of AD etiology pose considerable challenges for the translatability of these animal models, limiting their utility in drug development. This review offers a comprehensive analysis of widely employed rodent (mice and rats) and non-rodent models ( (zebrafish), , and ), detailing their phenotypic features and specific research applications. This review also examines the limitations inherent in these models and introduces various strategies for expanding AD modeling across diverse species, emphasizing recent advancement in non-human primates (NHPs) as valuable models. Furthermore, potential insights from the integration of innovative technologies in AD research are discussed, while providing valuable perspectives on the future development of AD animal models.
利用致病因素构建的动物模型显著推动了阿尔茨海默病(AD)的药物研发。这些主要的转基因模型主要在小鼠中,通过与家族性 AD 病例相关的基因突变来复制病理表型,因此成为评估药物疗效和进行机制研究的重要工具。然而,这些动物模型在物种特异性差异和 AD 病因的复杂性、异质性方面面临着相当大的挑战,限制了它们在药物研发中的应用。
本综述全面分析了广泛应用的啮齿动物(小鼠和大鼠)和非啮齿动物模型( (斑马鱼), ,和 ),详细介绍了它们的表型特征和特定的研究应用。本综述还检查了这些模型中固有的局限性,并介绍了在不同物种中扩展 AD 建模的各种策略,强调了最近在非人类灵长类动物(NHPs)中作为有价值模型的进展。此外,还讨论了将创新技术整合到 AD 研究中所带来的潜在见解,同时为 AD 动物模型的未来发展提供了有价值的观点。