期刊
ALZHEIMERS & DEMENTIA
卷 13, 期 9, 页码 1054-1067出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2017.02.003
关键词
Sleep; Neurofibrillary tangles; Amyloid beta; Memory consolidation; Frontohippocampal; Default mode network; Attractor systems
资金
- Alzheimer's Association [PCTRB-13-288476]
- American Brain Foundation
- J. D. French Alzheimer's Foundation
- Tau Consortium
- National Institutes of Health [K23 AG038357]
This perspective binds emerging evidence on the bidirectional relationship between Alzheimer's disease (AD) and sleep disorders through a model of brain rhythm attractor breakdown. This approach explains behavioral-cognitive changes in AD across the sleep-wake cycle and supports a causal association between early brainstem tau pathology and subsequent cortical amyloid beta accumulation. Specifically, early tau dysregulation within brainstem-hypothalamic nuclei leads to breakdown of sleep-wake attractor networks, with patients displaying an attenuated range of behavioral and electrophysiological activity patterns, a twilight zone of constant activity between deep rest and full alertness. This constant cortical activity promotes activity-dependent amyloid b accumulation in brain areas that modulate their activity across sleep-wake states, especially the medial prefrontal cortex. In addition, the accompanying breakdown of hippocampal-medial prefrontal cortex interplay across sleep stages could explain deficient memory consolidation through dysregulation of synaptic plasticity. Clinical implications include the potential therapeutic benefit of attractor consolidation (e.g., slow-wave sleep enhancers) in delaying AD progression. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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