Sleep deprivation leads to non-adaptive alterations in sleep microarchitecture and amyloid-β accumulation in a murine Alzheimer model
Neža Cankar,
Natalie Beschorner,
Anastasia Tsopanidou,
Filippa L. Qvist,
Ana R. Colaço,
Mie Andersen,
Celia Kjaerby,
Christine Delle,
Marius Lambert,
Filip Mundt,
Pia Weikop,
Mathias Jucker,
Matthias Mann,
Niels Henning Skotte,
Maiken Nedergaard
Affiliations
Neža Cankar
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Natalie Beschorner
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Anastasia Tsopanidou
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Filippa L. Qvist
NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Ana R. Colaço
Proteomics Research Infrastructure, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Mie Andersen
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Celia Kjaerby
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Christine Delle
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Marius Lambert
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Filip Mundt
NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Pia Weikop
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Mathias Jucker
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Matthias Mann
NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department for Proteomics and Signal Transduction, Max-Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
Niels Henning Skotte
NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Maiken Nedergaard
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA; Corresponding author
Summary: 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.
