Data_Sheet_1_Unraveling Early Signs of Navigational Impairment in APPswe/PS1dE9 Mice Using Morris Water Maze.zip

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.

轻度行为缺陷，系正常老化之组成部分，可作为即将来临的阿尔茨海默病的早期预示。本研究采用APPswe/PS1dE9（APP/PS1）阿尔茨海默病小鼠模型，运用Morris水迷宫空间学习范式，对疾病病理发生早期出现的轻度行为缺陷进行系统评估。传统行为分析显示，在该模型中，2个月大时空间记忆保持完好。在本研究中，我们采用了一种替代方法分析小鼠的行为，旨在通过关注水迷宫学习过程中的失败尝试，而非成功尝试，以更深入地理解认知缺陷的本质。与野生型小鼠相比，APP/PS1小鼠在训练初期表现出更多的失败尝试。然而，随着反复的尝试与错误，APP/PS1小鼠在训练后期达到的学习水平可与野生型小鼠相媲美。个体APP/PS1小鼠更倾向于采用一种非认知性搜索策略——旋转，这导致了学习过渡的突然变化以及失败尝试数量的增加。这些发现表明，微妙的中间指标作为诸如阿尔茨海默病等疾病的早期预示具有重要意义。