AUTHOR=Lee Yee Fun , Gerashchenko Dmitry , Timofeev Igor , Bacskai Brian J. , Kastanenka Ksenia V. 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00705

DOI=10.3389/fnins.2020.00705

ISSN=1662-453X

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. Alzheimer’s patients spend less time in NREM sleep and exhibit decreased slow wave activity. Consistent with the critical role of slow wave sleep in memory consolidation, reduced slow wave activity is associated with impaired memory consolidation in AD patients. The aberrant slow wave activity 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 presence of abundant oligomeric amyloid-beta. Optogenetic rescue of slow wave activity 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 slow wave activity disruptions that lead to further accumulations of amyloid and tau in AD. Moreover, since slow wave activity disruptions occur prior to the plaque deposition, slow wave activity disruptions provide an early biomarker for Alzheimer’s disease. Finally, we propose that therapeutic targeting of slow wave activity in AD might lead to an effective treatment for Alzheimer’s patients.