Early sleep and circadian markers of Alzheimer’s disease: The impact of APOE-ε4 on circadian rhythm and sleep-wake homeostasis in humans (360G-Wellcome-207799_Z_17_Z)

Sleep abnormalities are common in neurodegenerative disorders, and can be present long time before the clinical onset of the disease. This is true for Alzheimer’s disease (AD) as well, where the APOE-epsilon4 allele, a genetic predisposing factor for AD, has been recently correlated with impaired sleep in healthy adults. These data suggest a mechanistic contribution of sleep to neurodegeneration supported by its essential role in energetic restoration, neural plasticity and beta-amyloid clearance from the brain. Less is known as to how the circadian system and sleep-wake homeostasis are affected in AD and might interact in modulating or driving the onset and progression of disease, in particular in at-genetic-risk of AD (APOE) healthy participants. We plan to investigate for the first time the impact of the APOE genotype on the circadian system and the sleep-wake-homeostat and the way they interact in defining sleep and waking cognition in everyday life and under sleep laboratory conditions where we will experimentally modulate sleep pressure. This will help understand biological mechanisms linking cognitive deficits and sleep impairment in high-risk population for neurodegeneration, which in turn will pave the way for future intervention studies to improve sleep function and potentially delay disease onset.