Early sleep and circadian markers of Alzheimer’s disease: the impact of APOE-e4 on circadian rhythm and sleep-wake homeostasis in humans

Year of award: 2017


  • Dr Alpar Lazar

    University of East Anglia

Project summary

Sleep abnormalities are common in neurodegenerative disorders and can be present long before the clinical onset of disease. This is true for Alzheimer’s disease (AD) where the APOE ε4 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 about how the circadian system and sleep-wake homeostasis are affected in people with AD and how it might interact in modulating or driving the onset and progression of disease, in particular in healthy people who have a genetic risk of AD.

We plan to investigate the impact of the APOE genotype on the circadian system and sleep-wake homeostasis and the way they interact in defining sleep and waking cognition in everyday life and in a sleep laboratory where we will experimentally modulate sleep pressure.

This study will improve our understanding of biological mechanisms linking cognitive deficits and sleep impairment in people with a high risk of neurodegeneration, which in turn will pave the way for future intervention studies to improve sleep function and potentially delay disease onset.