The Research Institute of the McGill University Health Centre, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada.
The Research Institute of the McGill University Health Centre, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Departments of Biochemistry and Pharmacology and Therapeutics, McGill University, McIntyre Medical Sciences Bldg, 3655 Promenade Sir-William-Osler, room 1325, Montreal Quebec, Canada H3G 1Y6.
Alzheimers Res Ther. 2013 May 1;5(3):17. doi: 10.1186/alzrt171. eCollection 2013.
Alzheimer's disease (AD), for which there is no cure, is the most common form of dementia in the elderly. Despite tremendous efforts by the scientific community, the AD drug development pipeline remains extremely limited. Animal models of disease are a cornerstone of any drug development program and should be as relevant as possible to the disease, recapitulating the disease phenotype with high fidelity, to meaningfully contribute to the development of a successful therapeutic agent. Over the past two decades, transgenic models of AD based on the known genetic origins of familial AD have significantly contributed to our understanding of the molecular mechanisms involved in the onset and progression of the disease. These models were extensively used in AD drug development. The numerous reported failures of new treatments for AD in clinical trials indicate that the use of genetic models of AD may not represent the complete picture of AD in humans and that other types of animal models relevant to the sporadic form of the disease, which represents 95% of AD cases, should be developed. In this review, we will discuss the evolution of non-transgenic rat models of AD and how these models may open new avenues for drug development.
阿尔茨海默病（AD）是老年人最常见的痴呆症形式，目前尚无治愈方法。尽管科学界付出了巨大努力，但 AD 药物开发管道仍然极为有限。疾病动物模型是任何药物开发计划的基石，应尽可能与疾病相关，高度忠实地再现疾病表型，为成功治疗药物的开发做出有意义的贡献。在过去的二十年中，基于家族性 AD 已知遗传起源的 AD 转基因模型极大地促进了我们对疾病发病和进展中涉及的分子机制的理解。这些模型被广泛用于 AD 药物开发。大量新的 AD 治疗方法在临床试验中的失败表明，AD 的遗传模型的使用可能无法代表 AD 在人类中的全貌，应该开发与散发性 AD 相关的其他类型的动物模型，而散发性 AD 占 AD 病例的 95%。在这篇综述中，我们将讨论 AD 的非转基因大鼠模型的演变，以及这些模型如何为药物开发开辟新途径。
