Duke University Medical Center, Department of Medicine, Durham, NC 27710, USA.
CNS Neurol Disord Drug Targets. 2010 Aug;9(4):386-94. doi: 10.2174/187152710791556168.
Alzheimer's disease is a progressive, neurodegenerative disorder characterized by a devastating cognitive decline. The disease is identified pathologically by amyloid plaques composed of aggregated amyloid- peptide, neurofibrillary tangles composed of aggregated, hyperphosphorylated tau protein and neuron loss. While the disease was first described in 1906, transgenic mouse models for the study of Alzheimer's disease pathologies have only been available to scientists for fifteen years. Despite the generation of many different mouse models that develop amyloid plaques or neurofibrillary tangles, it has only been in recent years that mouse models demonstrating the two pathologies together have been made. Also, neuron loss has been difficult to achieve in many models. Most recently, several transgenic mouse lines have been generated that do demonstrate all three pathological characteristics of Alzheimer's disease: amyloid plaques, neurofibrillary tangles and neuron loss. This review will focus on the advances made in our understanding of Alzheimer's disease pathology using the transgenic mouse models. It will also discuss the limitations associated with studying some of these mice and how transgenic mouse models have contributed to the development of therapeutics for the treatment of Alzheimer's disease.
阿尔茨海默病是一种进行性神经退行性疾病，其特征是认知能力严重下降。该疾病在病理学上通过由聚集的淀粉样肽组成的淀粉样斑块、由聚集的过度磷酸化 tau 蛋白组成的神经原纤维缠结和神经元丢失来识别。虽然该疾病于 1906 年首次被描述，但用于研究阿尔茨海默病病理学的转基因小鼠模型仅在 15 年前才为科学家所获得。尽管已经产生了许多不同的发展淀粉样斑块或神经原纤维缠结的小鼠模型，但直到近年来才制造出同时具有这两种病理学特征的小鼠模型。此外，在许多模型中神经元丢失也很难实现。最近，已经产生了几种转基因小鼠系，它们确实表现出阿尔茨海默病的所有三种病理学特征：淀粉样斑块、神经原纤维缠结和神经元丢失。这篇综述将重点介绍使用转基因小鼠模型在我们对阿尔茨海默病病理学的理解方面取得的进展。它还将讨论研究其中一些小鼠的局限性以及转基因小鼠模型如何为阿尔茨海默病治疗药物的开发做出贡献。
