Key circuits through which sleep affects memory and their role in Alzheimer's disease

Abstract

Sleep is a critical physiological process for maintaining the cognitive function of brain, particularly about memory consolidation. This review systematically elaborates on the multiscale regulatory mechanisms of the sleep-wake cycle, with a focus on the neural circuits involved in sleep-dependent memory consolidation, such as the hippocampus-prefrontal-thalamus network, characteristic neural oscillations, and microglia-mediated synaptic changes. Building upon these foundations, the article delves into Alzheimer's disease (AD), providing an in-depth analysis of the complex bidirectional relationship between sleep disturbances and the core pathologies of AD. Early vulnerable brain regions in AD, including the entorhinal cortex, hippocampus, thalamus, and locus coeruleus, coincide precisely with key hubs of the sleep-memory circuitry. Pathological damage in these regions leads to disrupted sleep architecture and impaired memory consolidation, creating a vicious cycle that accelerates memory impairment and cognitive decline. Interventions targeting the sleep-memory circuitry may thus offer a promising new strategy for early intervention in AD.