Slow Wave Sleep Is a Promising Intervention Target for Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is the major cause of dementia, characterized by the presence of amyloid-beta plaques and neurofibrillary tau tangles. Plaques and tangles are associated with sleep-wake cycle disruptions, including the disruptions in non-rapid eye movement (NREM) slow wave sleep (SWS). Alzheimer's patients spend less time in NREM sleep and exhibit decreased slow wave activity (SWA). Consistent with the critical role of SWS in memory consolidation, reduced SWA is associated with impaired memory consolidation in AD patients. The aberrant SWA can be modeled in transgenic mouse models of amyloidosis and tauopathy. Animal models exhibited slow wave impairments early in the disease progression, prior to the deposition of amyloid-beta plaques, however, in the presence of abundant oligomeric amyloid-beta. Optogenetic rescue of SWA successfully halted the amyloid accumulation and restored intraneuronal calcium levels in mice. On the other hand, optogenetic acceleration of slow wave frequency exacerbated amyloid deposition and disrupted neuronal calcium homeostasis. In this review, we summarize the evidence and the mechanisms underlying the existence of a positive feedback loop between amyloid/tau pathology and SWA disruptions that lead to further accumulations of amyloid and tau in AD. Moreover, since SWA disruptions occur prior to the plaque deposition, SWA disruptions may provide an early biomarker for AD. Finally, we propose that therapeutic targeting of SWA in AD might lead to an effective treatment for Alzheimer's patients.

Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier

“…[ 42 ]. Taking into account all of the above, we suppose that slow wave sleep may be potential biomarker of AD that also have been discussed in other reviews [ 23 , 42 ].…”

“…Conversely, preceding daytime nap is accompanied by a reduction of the SWA time during subsequent nocturnal sleep [ 22 ]. The nature of SWA is not recognized yet, but there are growing body of evidence that SWA plays an important role in regulation of quality of sleep and in its restorative and clearing functions [ 10 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The sleep efficiency and depth are directly related to SWA [ 25 , 26 , 30 , 31 , 32 , 33 ].…”

“…The sleep efficiency and depth are directly related to SWA [ 25 , 26 , 30 , 31 , 32 , 33 ]. NREM SWA considered as a promising intervention target for AD [ 23 ]. SWA sleep plays crucial role in memory consolidation and the SWA disturbances are associated with AD in patients and animal models [ 23 ].…”

“…NREM SWA considered as a promising intervention target for AD [ 23 ]. SWA sleep plays crucial role in memory consolidation and the SWA disturbances are associated with AD in patients and animal models [ 23 ]. Studies in animal models have found decreased SWA in P301S tau transgenic mice [ 34 ].…”

“…Obviously, in the next couple of decades, the main strategies for a treatment of AD will be non-invasive methods of stimulation of clearance of the toxic A from the brain. The enhancement of SWA sleep is discussed as a promising tool in therapy of AD and rescue sleep-dependent memory consolidation [ 23 ].…”