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Early sleep and circadian disturbances in Alzheimer’s disease: The effect of APOE- ε4 on sleep and cognition throughout the circadian cycle (LazarU17SF)

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Sleep abnormalities are common features of 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-ε4 allele, a genetic predisposing factor for AD, has been recently correlated with impaired quality of 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.

Application deadline is 31st July 2018.

For more information on the supervisor for this project, please go here: https://www.uea.ac.uk/health-sciences/people/profile/a-lazar
Type of programme: PhD.
Start date of project: Flexible.
Mode of study: Full time.

Acceptable first degrees: Psychology, Health related subject.
The standard minimum entry requirement is 2:1 or above.

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at View Website.

A bench fee may also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Musiek ES, Holtzman DM: Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science (New York, NY) 2016, 354(6315):1004-1008.
ii) Videnovic A, Lazar AS, Barker RA, Overeem S. 'The clocks that time us'-circadian rhythms in neurodegenerative disorders. Nat Rev Neurol. 2014 Dec;10(12):683-93

iii) Lazar AS, Panin F, Goodman AO, Lazic SE, Lazar ZI, Mason SL, Rogers L, Murgatroyd PR,
Watson LP, Singh P et al: Sleep deficits but no metabolic deficits in premanifest Huntington's disease. Annals of neurology 2015, 78(4):630-648.

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