Sleep and Neurodegeneration: Examining Potential Physiological Mechanisms

The purpose of this review is to provide an overview of potential mechanisms mediating the bi-directional relationship between sleep and neurodegenerative diseases such as Alzheimer’s disease. We provide updates on previously proposed mechanisms and identify new mechanisms particularly concerning how sleep disturbances affect memory-related neural circuits. In this review, we focus on the multiple mechanisms that potentially mediate the relationship between sleep and Alzheimer’s disease. We present updates for previously hypothesized mechanisms such as sleep-related changes in production/release and clearance of amyloid-β and tau proteins as well as more recently proposed mechanisms relating to tau phosphorylation, the orexin system, astrocytes, and microglia. We also highlight how disruptions in sleep EEG oscillations that underlie memory-related neural circuits, such as slow wave activity, theta bursts, sleep spindles, and gamma ripples, change in Alzheimer’s disease. Disturbed sleep increases Alzheimer’s disease risk via multiple potential mechanisms that suggest multiple targets to test approved and effective treatments of sleep disorders to prevent or delay Alzheimer’s disease.