Implication of the thalamus in sleep alterations observed in Alzheimer's disease

Alzheimer's disease (AD), the most common neurodegenerative disorder, is frequently accompanied by sleep disturbances. Alterations of sleep, in both quality and quantity, contribute to the progression of AD neuropathology. The thalamus, through its diverse nuclei, plays a central role in sleep regulation and sleep-dependent memory consolidation, making it a relevant structure to investigate sleep disturbances associated with AD. Structural studies reveal that AD-related changes emerge early within the thalamus: Higher-order nuclei show atrophy, degeneration, and tau and Aβ accumulation. AD is also associated with functional and connectivity impairments involving the thalamus. Moreover, the thalamus plays a major role in generating, propagating, and synchronizing sleep oscillations, which are crucial for sleep-dependent memory, and alterations of the thalamus are linked with cognitive decline in AD. Thus, here we highlight this structure as a promising therapeutic target for restoring sleep physiology and cognitive function in AD.