Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.

阿尔茨海默病 (AD) 的执行功能缺陷发生在疾病进展的早期，并且可能预示着认知能力下降。然而，没有临床前研究发现在常用的 APPSwe/PS1ΔE9 (APP/PS1) 小鼠模型中存在奖励执行功能缺陷。为了解决这个问题，我们评估了 12-26 个月大的 APP/PS1 小鼠的奖励逆转和/或灭绝任务。16 个月大，但不是 13 或 26 个月大的 APP/PS1 小鼠的灭绝率降低。在 22 个月大但不是 13 个月大的 APP/PS1 动物中观察到逆转缺陷。然后，我们确认逆转障碍与先前报道的 AD 小鼠模型和人类的视觉障碍无关。年龄，但不是基因型，对视网膜健康的标志物有显着影响，表明在 APP/PS1 小鼠中看到的缺陷与认知直接相关。这是 APP/PS1 小鼠奖励执行功能的首次表征，具有促进从临床前模型到临床的转化的巨大潜力。