Blackmer-Raynolds Lisa, Lipson Lyndsey D, Fraccaroli Isabel, Krout Ian N, Chang Jianjun, Sampson Timothy Robert
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA.
School of Biological Sciences, Neuroscience Undergraduate Program, Georgia Institute of Technology, Atlanta, 30332, Georgia, USA.
Sci Rep. 2025 Feb 7;15(1):4631. doi: 10.1038/s41598-025-89051-8.
APP knock-in (KI) mice serve as an exciting new model system to understand amyloid beta (Aβ) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APP mouse model (containing the humanized APP with three familial Alzheimer's disease mutations) and the APP control (containing wildtype humanized APP) are the first commercially available APP KI mice within the United States. While APP mice have been shown to develop progressive Aβ pathology and neuroinflammation, the age at which behavioral and cognitive impairments begin to develop has yet to be described. Therefore, we performed an in-depth longitudinal study over 16 months, assessing cognition in these two strains, as well as assessments of motor function. While no cognitive deficits are observed in either genotype throughout the first year of life, 16-month-old APP, but not APP mice show initial signs of spatial memory decline. In addition, both genotypes display impaired motor function at the same age. Together, this data identifies a timeframe where behavioral deficits appear, providing an essential foundation for future studies using these model systems.
淀粉样前体蛋白（APP）基因敲入（KI）小鼠是一种令人兴奋的新型模型系统，用于理解β-淀粉样蛋白（Aβ）病理学，克服了先前基于过表达的模型系统的许多局限性。APP小鼠模型（包含具有三种家族性阿尔茨海默病突变的人源化APP）和APP对照（包含野生型人源化APP）是美国首批可商购的APP KI小鼠。虽然已证明APP小鼠会出现进行性Aβ病理学和神经炎症，但行为和认知障碍开始出现的年龄尚未得到描述。因此，我们进行了一项为期16个月的深入纵向研究，评估这两个品系的认知能力以及运动功能。在生命的第一年，两种基因型均未观察到认知缺陷，但16个月大的APP小鼠而非对照小鼠显示出空间记忆下降的初始迹象。此外，两种基因型在相同年龄时均表现出运动功能受损。这些数据共同确定了行为缺陷出现的时间框架，为未来使用这些模型系统的研究提供了重要基础。
