0225 Effect of thermoneutral temperature exposure in the APP/PS1 knock-in mouse model of Alzheimer’s disease

Abstract

Abstract Introduction There is growing evidence that disordered sleep in Alzheimer’s disease (AD) may accelerate neuropathology, thus promoting a vicious cycle. In a previous study, we found that improving sleep through thermoneutral ambient temperature exposure may slow disease progression in 3xTg-AD mice. However, the confounding effects of temperature on metabolism in addition to sleep remained an open question. Methods To test whether the effect of thermoneutral warming on amyloid pathology is mediated by sleep changes rather than other non-specific physiologic effects of temperature, we conducted a new study on APP/PS1 knock-in (KI) mice. First, 6-m.o. male APP/PS1-KI mice were instrumented for EEG/EMG sleep analysis. After a week-long baseline recording, we split the mice into 4 separate groups: 1. SE (n=8), which were exposed to 30°C thermoneutral ambient temperature during the 12-hour light period; 2. SE-SD (n=9), which received sleep disruption through mild intermittent cage vibration alongside thermoneutral temperature exposure; 3. SD (n=8), which received sleep disruption at room temperature (22°C); and 4. CTRL (n=8), which were undisturbed and at room temperature. This design aims to decouple the sleep-enhancing effect of thermoneutral exposure from other non-specific effects. After four weeks of treatment, the animals were euthanized and the brains dissected to assay Aβ levels by ELISA. Vigilance states, i.e., Wake, REM, NREM, and slow wave sleep (SWS) within NREM – were scored in 4-second epochs from the EEG/EMG recordings and sleep metrics computed. Results Initial analysis of sleep revealed some SE-induced increases in SWS similar to our findings in 3xTg-AD mice. Sleep disruption reduces SWS even when thermoneutral warming occurs. Biochemical assays are in progress to reveal the treatment effects on Aβ levels in the brain. Conclusion Sleep disruption through vibration seems to be an effective way to negate the sleep-specific effect of thermoneutral temperature exposure. Incorporation of the biochemical assay data will help uncover the correlation between SWS and AD progression. Support (if any) R01AG068215