Sleep and β-amyloid deposition in Alzheimer disease: Insights on mechanisms and possible innovative treatments

Susanna Cordone, Ludovica Annarumma, Paolo Maria Rossini, Luigi De Gennaro

Research output: Contribution to journalReview articlepeer-review


The growing interest in the preclinical stage of Alzheimer's disease (AD) led investigators to identify modifiable risk and predictive factors useful to design early intervention strategies. The preclinical stage of AD is characterized by β-amyloid (Aβ) aggregation into amyloid plaques and tau phosphorylation and aggregation into neurofibrillary tangles. There is a consensus on the importance of sleep within this context: the bidirectional relationship between sleep and AD pathology is supported by growing evidence that proved that the occurrence of sleep changes starting from the preclinical stage of AD, many years before the onset of cognitive decline. Hence, we review the most recent studies on sleep disturbances related to Aβ and the effects of sleep deprivation on Aβ accumulation in animal and human models. We also discuss evidence on the role of sleep in clearing the brain of toxic metabolic by-products, with original findings of the clearance activity of the glymphatic system stimulated by sleep. Furthermore, starting from new recent advances about the relationship between slow-wave sleep (SWS) and Aβ burden, we review the results of recent electroencephalographic (EEG) studies in order to clarify the possible role of SWS component disruption as a novel mechanistic pathway through which Aβ pathology may contribute to cognitive decline and, conversely, the eventual useful role of SWS in facilitating Aβ clearance. Finally, we discuss some promising innovative, effective, low-risk, non-invasive interventions, although empirical evidence on the efficacy of sleep interventions in improving the course of AD is at the very beginning.

Original languageEnglish
Article number695
JournalFrontiers in Pharmacology
Issue numberJUN
Publication statusPublished - Jan 1 2019


  • Alzheimer's disease
  • Glymphatic system
  • Sleep
  • Slow-wave activity
  • β-amyloid

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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