Chronic sleep fragmentation exacerbates amyloid β deposition in Alzheimer's disease model mice

Eiko N Minakawa; Koyomi Miyazaki; Kazushi Maruo; Hiroko Yagihara; Hiromi Fujita; Keiji Wada; Yoshitaka Nagai

doi:10.1016/j.neulet.2017.05.054

Chronic sleep fragmentation exacerbates amyloid β deposition in Alzheimer's disease model mice

Neurosci Lett. 2017 Jul 13:653:362-369. doi: 10.1016/j.neulet.2017.05.054. Epub 2017 May 26.

Authors

Eiko N Minakawa¹, Koyomi Miyazaki², Kazushi Maruo³, Hiroko Yagihara⁴, Hiromi Fujita⁵, Keiji Wada⁶, Yoshitaka Nagai⁷

Affiliations

¹ Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address: minakawa@ncnp.go.jp.
² Physiologically Active Substances Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan. Electronic address: k-miyazaki@aist.go.jp.
³ Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8551, Japan. Electronic address: maruo@ncnp.go.jp.
⁴ Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address: bonkobara@ncnp.go.jp.
⁵ Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address: hfujita@ncnp.go.jp.
⁶ Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan; Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8551, Japan. Electronic address: wada@ncnp.go.jp.
⁷ Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan; Department of Neurotherapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: nagai@neurother.med.osaka-u.ac.jp.

PMID: 28554860
DOI: 10.1016/j.neulet.2017.05.054

Abstract

Sleep fragmentation due to intermittent nocturnal arousal resulting in a reduction of total sleep time and sleep efficiency is a common symptom among people with Alzheimer's disease (AD) and elderly people with normal cognitive function. Although epidemiological studies have indicated an association between sleep fragmentation and elevated risk of AD, a relevant disease model to elucidate the underlying mechanisms was lacking owing to technical limitations. Here we successfully induced chronic sleep fragmentation in AD model mice using a recently developed running-wheel-based device and demonstrate that chronic sleep fragmentation increases amyloid β deposition. Notably, the severity of amyloid β deposition exhibited a significant positive correlation with the extent of sleep fragmentation. These findings provide a useful contribution to the development of novel treatments that decelerate the disease course of AD in the patients, or decrease the risk of developing AD in healthy elderly people through the improvement of sleep quality.

Keywords: Alzheimer’s disease; Amyloid β; Neurodegenerative diseases; Sleep disturbance; Sleep fragmentation.

MeSH terms

Alzheimer Disease / complications
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism*
Animals
Disease Models, Animal
Mice
Mice, Inbred C57BL
Sleep Deprivation / metabolism*
Sleep Wake Disorders / etiology
Sleep Wake Disorders / metabolism*

Substances

Amyloid beta-Peptides