Sleep deprivation leads to non-adaptive alterations in sleep microarchitecture and amyloid-β accumulation in a murine Alzheimer model
Impaired sleep is a common aspect of aging and often precedes the onset of Alzheimer's disease. Here, we compare the effects of sleep deprivation in young wild-type mice and their APP/PS1 littermates, a murine model of Alzheimer's disease. After 7 h of sleep deprivation, both genotypes exhibit an increase in EEG slow-wave activity. However, only the wild-type mice demonstrate an increase in the power of infraslow norepinephrine oscillations, which are characteristic of healthy non-rapid eye movement sleep. Notably, the APP/PS1 mice fail to enhance norepinephrine oscillations 24 h after sleep deprivation, coinciding with an accumulation of cerebral amyloid-β protein. Proteome analysis of cerebrospinal fluid and extracellular fluid further supports these findings by showing altered protein clearance in APP/PS1 mice. We propose that the suppression of infraslow norepinephrine oscillations following sleep deprivation contributes to increased vulnerability to sleep loss and heightens the risk of developing amyloid pathology in early stages of Alzheimer's disease.
Authors
- Ana R. Colaço
- Mathias Jucker (ORCID: https://orcid.org/0000-0001-9045-1072)
- Pia Weikop (ORCID: https://orcid.org/0000-0002-8422-1702)
- Mie Andersen (ORCID: https://orcid.org/0000-0002-6978-585X)
- Filip Mundt (ORCID: https://orcid.org/0000-0001-8622-2971)
- Marius Lambert
- Neža Cankar (ORCID: https://orcid.org/0009-0008-3736-2095)
- Natalie Beschörner (ORCID: https://orcid.org/0000-0002-2732-5169)
- Niels H. Skotte (ORCID: https://orcid.org/0000-0001-7027-7193)
- Filippa L Qvist (ORCID: https://orcid.org/0000-0002-6512-0957)
- Christine Delle
- Anastasia Tsopanidou
- Celia Kjærby (ORCID: https://orcid.org/0000-0003-1106-9217)
- Maiken Nedergaard (ORCID: https://orcid.org/0000-0001-6502-6031)
- Matthias Mann (ORCID: https://orcid.org/0000-0003-1292-4799)
Institutions
- University of Copenhagen (DK)
- Novo Nordisk Foundation (DK)
- Hertie Institute for Clinical Brain Research (DE)
- University of Tübingen (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114977
- Citations
- 24
- Primary Topic
- Sleep and Wakefulness Research
- Type
- article
- Field-Weighted Citation Impact
- 8.22
Funders
- U.S. Department of Defense
- Foundation for the National Institutes of Health
- Simons Foundation
- Cure Alzheimer's Fund
- EU Joint Programme – Neurodegenerative Disease Research
- Adelson Family Foundation
- Human Frontier Science Program
- Lundbeckfonden
- Novo Nordisk
- Novo Nordisk Fonden
- H. Lundbeck A/S
- National Institutes of Health
- Army Research Office