Bidirectional relationships between sleep and amyloid-beta in the hippocampus

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by progressive hippocampal-dependent explicit memory deficits that begin at the onset of the illness. An early hallmark of AD is the accumulation of amyloid-beta (Aß) proteins in brain structures involved in encoding and consolidation of memory, like the hippocampus and prefrontal cortex. Aß neurotoxicity is known to induce synaptic dysfunctions and neuronal death leading to cognitive decline. Another recurrent event observed in AD is sleep disturbances. Decreased sleep duration, sleep fragmentation, and circadian alterations are often observed in early AD. The origin of these disturbances, and especially the specific contribution of the hippocampal Aß pathology, remains to be determined. It is required to identify mechanisms impacting wakefulness and sleep architecture and microarchitecture given the role of sleep in memory encoding and consolidation. Sleep perturbations in AD are thus likely contributing to memory decline in the course of the disease. The central aim of this review is to address the bidirectional relationship between sleep and hippocampal Aß by discussing the literature featuring data on wakefulness and sleep variables (i.e., duration, electroencephalographic activity, daily distribution) in AD mouse models and on the effect of enforced sleep loss on Aß pathology in the hippocampus. The current state of knowledge on this topic emphasizes a clear need for more efforts to assess the precise impact of hippocampal Aß on wakefulness and sleep quality as well as the mechanisms mediating their reciprocal relationship.

Keywords: Alzheimer’s disease; Amyloid-beta oligomers; Electroencephalographic activity; Mouse models; Sleep architecture; Sleep fragmentation.