title: Brain rhythm attractor breakdown in Alzheimer's disease: Functional and pathologic implications.
abstract: 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 β 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 β 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.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Neurological Institute of Athens, Athens, Greece. Electronic address: Elissaios.Karageorgiou@ucsf.edu.
authors.forename: Elissaios
authors.initials: E
authors.lastname: Karageorgiou
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D016874:Neurofibrillary Tangles / Q000473:pathology; D012893:Sleep Wake Disorders / Q000209:etiology*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Amyloid β; Attractor systems; Default mode network; Frontohippocampal; Memory consolidation; Neurofibrillary tangles; Sleep