Alzheimer's Disease and Sleep-Wake Disturbances: Amyloid, Astrocytes, and Animal Models

Sleep-wake abnormalities arecommonin patients with Alzheimer's disease, and can be a major reason for institutionalization. However, an emerging concept is that these sleep-wake disturbances are part of the causal pathway accelerating the neurodegenerative process. Recently, new findings have provided intriguing evidence for a positive feedback loop between sleep-wake dysfunction and beta-amyloid (A beta) aggregation. Studies in both humans and animal models have shown that extended periods of wakefulness increase A beta levels and aggregation, and accumulation of A beta causes fragmentation of sleep. This perspective is aimed at presenting evidence supporting causal links between sleep-wake dysfunction and aggregation of A beta peptide in Alzheimer's disease, and explores the role of astrocytes, a specialized type of glial cell, in this context underlying Alzheimer's disease pathology. The utility of current animal models and the unexplored potential of alternative animal models for testing mechanisms involved in the reciprocal relationship between sleep disruption and A beta are also discussed.