%0 Journal Article
%T Sleep in Alzheimer's Disease¨CBeyond Amyloid
%A David M. Holtzman
%A Jerrah K. Holth
%A Tirth K. Patel
%J Archive of "Neurobiology of Sleep and Circadian Rhythms".
%D 2017
%R 10.1016/j.nbscr.2016.08.002
%X 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 ¦Â (A¦Â) has been well established with disturbed sleep and increased wakefulness leading to increased A¦Â production and decreased A¦Â clearance; whereas A¦Â deposition is associated with increased wakefulness and sleep disturbances. A¦Â fluctuates with the sleep-wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with A¦Â deposition, likely due to its sequestration into amyloid plaques. As such, A¦Â is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phases of AD. In addition to A¦Â, 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
%K A¦Â
%K amyloid ¦Â
%K AD
%K Alzheimer's disease
%K APP
%K amyloid precursor protein
%K BF
%K basal forebrain
%K bvFTD
%K behavioral variant FTD
%K CBD
%K corticobasal degeneration
%K CSF
%K cerebrospinal fluid
%K DLB
%K dementia with Lewy bodies
%K DR
%K dorsal raphe
%K EDS
%K excessive daytime sleepiness
%K EEG
%K electroencephalography
%K FTD
%K Frontotemporal Dementia
%K htau
%K human tau
%K ISF
%K interstitial fluid
%K LC
%K locus coeruleus
%K LDT
%K laterodorsal tegmental nucleus
%K LH
%K lateral hypothalamus
%K mPB
%K medial parabrachial nucleus
%K NBM
%K nucleus basalis of Meynert
%K NFT
%K neurofibrillary tangle
%K NREM
%K non-rapid eye movement
%K PAG
%K periaqueductal gray matter
%K PLMD
%K periodic limb movement disorder
%K PPT
%K pedunculopontine tegmental nucleus
%K PSP
%K progressive supranuclear palsy
%K PFZ
%K parafacial zone
%K RBD
%K REM sleep behavior disorder
%K REM
%K rapid eye movement
%K SCN
%K suprachiasmatic nucleus
%K SLD
%K sublaterodorsal area
%K SWS
%K slow wave sleep
%K TMN
%K tuberomammillary nucleus
%K VLPO
%K ventrolateral preoptic nucleus
%K vPAG
%K ventral periaqueductal gray Alzheimer's disease
%K Sleep
%K Amyloid
%K Tau
%K Alpha-synuclein
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312809/