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Sleep in Alzheimer's Disease–Beyond Amyloid

Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well es...

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Autores principales: Holth, Jerrah K., Patel, Tirth K., Holtzman, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312809/
https://www.ncbi.nlm.nih.gov/pubmed/28217760
http://dx.doi.org/10.1016/j.nbscr.2016.08.002
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author Holth, Jerrah K.
Patel, Tirth K.
Holtzman, David M.
author_facet Holth, Jerrah K.
Patel, Tirth K.
Holtzman, David M.
author_sort Holth, Jerrah K.
collection PubMed
description Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep-wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with Aβ deposition, likely due to its sequestration into amyloid plaques. As such, Aβ is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phases of AD. In addition to Aβ, the influence of tau AD pathology is likely important to the sleep disturbances observed in AD. Abnormal tau is the earliest observable AD-like pathology in the brain with abnormal tau phosphorylation in many sleep regulating regions such as the locus coeruleus, dorsal raphe, tuberomammillary nucleus, parabrachial nucleus, and basal forebrain prior to the appearance of amyloid or cortical tau pathology. Furthermore, human tau mouse models exhibit AD-like sleep disturbances and sleep changes are common in other tauopathies including frontotemporal dementia and progressive supranuclear palsy. Together these observations suggest that tau pathology can induce sleep disturbances and may play a large role in the sleep disruption seen in AD. To elucidate the relationship between sleep and AD it will be necessary to not only understand the role of amyloid but also tau and how these two pathologies, together with comorbid pathology such as alpha-synuclein, interact and affect sleep regulation in the brain.
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spelling pubmed-53128092018-01-01 Sleep in Alzheimer's Disease–Beyond Amyloid Holth, Jerrah K. Patel, Tirth K. Holtzman, David M. Neurobiol Sleep Circadian Rhythms Article Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep-wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with Aβ deposition, likely due to its sequestration into amyloid plaques. As such, Aβ is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phases of AD. In addition to Aβ, the influence of tau AD pathology is likely important to the sleep disturbances observed in AD. Abnormal tau is the earliest observable AD-like pathology in the brain with abnormal tau phosphorylation in many sleep regulating regions such as the locus coeruleus, dorsal raphe, tuberomammillary nucleus, parabrachial nucleus, and basal forebrain prior to the appearance of amyloid or cortical tau pathology. Furthermore, human tau mouse models exhibit AD-like sleep disturbances and sleep changes are common in other tauopathies including frontotemporal dementia and progressive supranuclear palsy. Together these observations suggest that tau pathology can induce sleep disturbances and may play a large role in the sleep disruption seen in AD. To elucidate the relationship between sleep and AD it will be necessary to not only understand the role of amyloid but also tau and how these two pathologies, together with comorbid pathology such as alpha-synuclein, interact and affect sleep regulation in the brain. Elsevier 2016-08-10 /pmc/articles/PMC5312809/ /pubmed/28217760 http://dx.doi.org/10.1016/j.nbscr.2016.08.002 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Holth, Jerrah K.
Patel, Tirth K.
Holtzman, David M.
Sleep in Alzheimer's Disease–Beyond Amyloid
title Sleep in Alzheimer's Disease–Beyond Amyloid
title_full Sleep in Alzheimer's Disease–Beyond Amyloid
title_fullStr Sleep in Alzheimer's Disease–Beyond Amyloid
title_full_unstemmed Sleep in Alzheimer's Disease–Beyond Amyloid
title_short Sleep in Alzheimer's Disease–Beyond Amyloid
title_sort sleep in alzheimer's disease–beyond amyloid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312809/
https://www.ncbi.nlm.nih.gov/pubmed/28217760
http://dx.doi.org/10.1016/j.nbscr.2016.08.002
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