Protein that wakes up the brain could provide target for Alzheimer's prevention
In recent years, research has linked sleep problems to Alzheimer’s disease. This relationship involves a neurotransmitter called orexin that awakens the brain from sleep and has been shown to be heightened in moderate to severe sufferers of Alzheimer’s. New research conducted at Washington University in St Louis suggests that removing the orexin protein in mice enables them to sleep longer, which could serve to hinder development of the disease.
One of the ways that the orexin protein and sleep loss can lead to Alzheimer’s is through enabling the development of brain plaques. These build up before and during the onset of Alzheimer’s and correlate with the development of symptoms like memory loss and disorientation, leading scientists to believe that halting their buildup may go some way to combating the disease.
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Putting this theory to the test, the researchers used mice that were genetically engineered to possess elevated amyloid beta, the protein that helps to make up brain plaques. By breeding these mice with other mice lacking the orexin protein, the researchers found the offspring had less sleep problems and developed around half as many plaques.
Mice with no orexin slept for around an hour extra during twelve-hour observation periods, while mice with orexin were more lively. Conversely, when the researchers heightened orexin levels, the mice stayed awake for longer and grew more plaques. Another noteworthy finding was that manipulating orexin levels in a section of the brain unrelated to the mouse's ability to sleep had no bearing on levels of plaque.
"The fact that orexin can only affect plaques when it also affects sleep means we will have to think carefully about how to target it for Alzheimer’s prevention," says David Holtzman, head of the university's Department of Neurology and senior author of the research paper. "But the declines in plaque levels that we saw in the mice were very strong, so we’re still very interested in exploring its potential for reducing risk.”
Holtzman and his team are now exploring the impacts of sleep medications on the build up of brain plaques in humans.
The research is set to be published in the November 24 issue of the Journal of Experimental Medicine.