Sex differences in sleep fragmentation in 5xFAD mice.
Kaitlyn Kim1, Angel-Rose L Villegas2, Amanda R Kelley1
1Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, United States; Department of Biochemistry and Biophysics, College of Science, Oregon State University, Corvallis, OR 97331, United States.
Neuroscience
|October 25, 2025
Summary
Early sleep changes in Alzheimer's disease (AD) models suggest disruptions are preclinical markers. These sex-specific sleep alterations in 5xFAD mice indicate potential early detection methods for AD pathology.
Area of Science:
- Neuroscience
- Sleep Medicine
- Genetics
Background:
- Sleep alterations are linked to Alzheimer's disease (AD), but their role as an early symptom or later development is unclear.
- Investigating sleep changes in transgenic mouse models can provide insights into early AD pathology.
Purpose of the Study:
- To determine if sleep alterations are an early symptom of Alzheimer's disease (AD) pathology.
- To assess sex-specific differences in sleep patterns in a mouse model of AD.
Main Methods:
- Utilized 5xFAD heterozygous (Het) mice and wild-type (WT) littermates at various ages (1-6 months).
- Noninvasively scored 3-state sleep during the dark cycle using respirations and body movements in instrumented home cages.
- Assessed sleep architecture, including fragmentation, microarousals, wake time, and REM sleep parameters.
Main Results:
- Progressive sleep architecture alterations, including increased sleep fragmentation and microarousals, were observed in Het mice as early as 1 month of age.
- Het mice showed increased wake time and decreased total sleep time and REM sleep latency compared to WT controls.
- These genotype differences were more pronounced in females and widened with age, suggesting sex-specific and early-onset pathology.
Conclusions:
- Early, sex-specific disruptions in dark cycle sleep architecture occur in a mouse model of AD.
- These sleep dysregulations, potentially linked to amyloid-beta oligomer accumulation, may serve as preclinical markers for AD.
- Findings highlight the importance of considering sex differences in early AD research and potential diagnostic strategies.
