Delayed daily activity and reduced NREM slow-wave power in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is associated with disrupted circadian rhythms and sleep, which are thought to reflect an impairment of internal circadian timekeeping that contribute to clinical symptoms and disease progression. To evaluate these hypotheses, a suitable preclinical model of AD is needed. We performed a comprehensive assessment of circadian rhythms and sleep in the APP/PS1(APP/PS1) mouse model using long-term in vivo electroencephalogram (EEG) monitoring and behavioral assays from 5 to 22 months of age. APP/PS1 mice were crossed with a PERIOD2::LUCIFERASE (PER2::LUC) mouse model to evaluate synchrony among peripheral circadian oscillators. The APP/PS1 mice exhibited a mild but persistent phase delay of nocturnal activity onset in 12:12h light:dark conditions, as well as a shift toward higher frequencies in the EEG power spectra compared to littermate controls. Our results suggest that APP/PS1 mice may not be the optimal preclinical model for studying the specific circadian changes associated with AD but that quantitative EEG may offer a sensitive measure of AD-associated changes in sleep quality that can be modeled in APP/PS1 mice.