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

doi:10.3389/fphar.2019.00695

Abstract

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.

Highlights

Alzheimer’s disease (AD) is the most common cause of dementia and represents one of the most dramatic challenges of modern society
The results show that high obstructive sleep apnea (OSA) indexes were related to higher Aβ levels measured by PiB-PET scans and the increasing in Aβ levels progressively augmented across time (2 years’ follow-up)
Aβ42 levels in a different time of the day were significantly different between the two groups in contrast to Aβ40 and tau protein levels that remained stable. These results suggest that sleep deprivation (SD) could interfere with the physiological decrement in Aβ42 levels measured in the morning, and it elevates the risk of AD

Summary

INTRODUCTION

Alzheimer’s disease (AD) is the most common cause of dementia and represents one of the most dramatic challenges of modern society. Starting from the assumption that sleep loss has an important negative implication in cognitive impairment, the most recent contributions of animal and human models in the field of AD are extending their focus on other interesting methodological and conceptual issues: i) scheduling different long-term SD periods; ii) investigating different subtypes of cognitive impairments; iii) testing the irreversibility of these impairments, by utilizing longitudinal experimental protocols; iv) increasing the use of non-genetically predisposed mouse model to better replicate adult-elderly individuals; v) considering sleep loss as a “stressor”; vi) investigating possible neuronal mechanisms implied in sleep– Aβ relationship; and vii) considering the possible role of glia in AD pathogenic mechanisms

Animal Models

Human Models

POSSIBLE INNOVATIVE TREATMENTS

Findings

CONCLUDING REMARKS