Overview of Transgenic Mouse Models for Alzheimer's Disease.
Overview of Transgenic Mouse Models for Alzheimer's Disease.
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DOI：
10.1002/cpns.81
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发表时间：
2019-09-01
影响因子：
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通讯作者：
McGonigle, Paul
中科院分区：
文献类型：
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作者：
Myers, Ariana;McGonigle, Paul
这篇综述描述了几种阿尔茨海默病（AD）的转基因小鼠模型，AD是一种破坏性的神经退行性疾病，导致进行性认知下降，并在死后通过大脑皮层中存在细胞外淀粉样蛋白β（Abeta）斑块和神经元内tau神经元缠结来诊断。目前还没有治疗、预防甚至减缓疾病进展的干预措施。其复杂的病因学和病理学对动物模型开发提出了重大挑战，并且没有单一模型忠实地概括AD的病理学方面和行为表型。已经产生了近200种AD的转基因啮齿动物模型，主要是基于与该疾病的家族形式中的Abeta蛋白质错误加工相关的突变。最近的模型包括tau蛋白的突变，以及与散发性疾病相关的突变。这里考虑了这些模型中最常用和最具特征的突出特征、优势、局限性和关键区别。虽然许多这些模型的翻译效用，以评估新的治疗方法的潜力是有争议的，不同的模型可用的知识和详细了解他们的功能可以帮助选择最佳的模型，探索疾病的机制或评估候选药物。考虑到最近的临床试验失败，我们评论这些模型的预测效用，并讨论了基于过去十年中产生的大量临床数据的AD模型开发的趋势和未来方向。John Wiley & Sons，Inc._关于我们
This review describes several transgenic mouse models of Alzheimer's disease (AD), a devastating neurodegenerative disorder that causes progressive cognitive decline and is diagnosed postmortem by the presence of extracellular amyloid-beta (Abeta) plaques and intraneuronal tau neurofibrillary tangles in the cerebral cortex. Currently there is no intervention that cures, prevents, or even slows disease progression. Its complex etiology and pathology pose significant challenges for animal model development, and there is no single model that faithfully recapitulates both the pathological aspects and behavioral phenotypes of AD. Nearly 200 transgenic rodent models of AD have been generated primarily based on mutations linked to Abeta protein misprocessing in the familial form of the disease. More recent models incorporate mutations in tau protein, as well as mutations associated with the sporadic form of the disease. The salient features, strengths, limitations, and key differentiators for the most commonly used and best characterized of these models are considered here. While the translational utility of many of these models to assess the potential of novel therapeutics is in dispute, knowledge of the different models available and a detailed understanding of their features can aid in the selection of the optimal model to explore disease mechanisms or evaluate candidate medications. We comment on the predictive utility of these models considering recent clinical trial failures and discuss trends and future directions in the development of models for AD based on the plethora of clinical data that have been generated over the last decade. © 2019 by John Wiley & Sons, Inc.