Alzheimer’s disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial AD (FAD) patients. Newer generations of mouse models through knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, have been developed for both familial and sporadic AD risk genes with the hope to more accurately model proteinopathies without over-expression of human AD genes in mouse brains. In this review, we summarized the phenotypes of a few commonly used as well as newly developed mouse models in translational research laboratories including the presence or absence of key pathological features of AD such as amyloid and tau pathology, synaptic and neuronal degeneration as well as cognitive and behavior deficits. In addition, advantages and limitations of these AD mouse models have been elaborated along with discussions of any sex-specific features. More importantly, the omics data from available AD mouse models have been analyzed to categorize molecular signatures of each model reminiscent of human AD brain changes, with the hope to guide future selection of most suitable models for specific research questions to be addressed in the AD field.

中文翻译：

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阿尔茨海默病小鼠模型的最新进展

阿尔茨海默病 (AD) 是美国 (US) 最常见的神经退行性疾病。动物模型，特别是小鼠模型的开发是为了更好地阐明疾病机制并测试 AD 的治疗策略。该领域的大部分工作集中在通过过度表达与家族性 AD (FAD) 患者相关的基因突变来开发转基因 (Tg) 小鼠模型。通过敲入 (KI)/敲除 (KO) 或 CRISPR 基因编辑技术，针对家族性和散发性 AD 风险基因开发了新一代小鼠模型，希望在不过度表达人类 AD 风险基因的情况下更准确地模拟蛋白质病。小鼠大脑中的 AD 基因。在这篇综述中，我们总结了转化研究实验室中一些常用和新开发的小鼠模型的表型，包括是否存在 AD 的关键病理特征，如淀粉样蛋白和 tau 蛋白病理、突触和神经元变性以及认知功能障碍。和行为缺陷。此外，还详细阐述了这些 AD 小鼠模型的优点和局限性，并讨论了任何性别特异性特征。更重要的是，我们对现有 AD 小鼠模型的组学数据进行了分析，对每个模型的分子特征进行了分类，让人想起人类 AD 大脑的变化，希望能够指导未来针对 AD 领域要解决的特定研究问题选择最合适的模型。