To view an abstract, select an author from the vertical list on the left.
2013 Grants - Wu
Mechanisms Underlying Sleep-Dependent Modulation of Abeta
Mark Wu, M.D., Ph.D.
Johns Hopkins University School of Medicine
2013 New Investigator Research Grant
Increasing age is a key risk factor in developing both Alzheimer's disease and sleep disorders. Because older people have changes in respiratory and other functions, they also tend to experience poor sleep. However, the links between sleep disorders and brain health have not been sufficiently explored.
In preliminary research, Mark Wu, M.D., Ph.D., and colleagues found that poor sleep may be related to Alzheimer's in two ways. First, people with Alzheimer's disease and mice with Alzheimer's-like brain changes have fragmented or decreased sleep. Second, sleep deprivation appears to increase the levels of beta-amyloid in both humans and mice. Beta-amyloid is a protein fragment that may play a key role in dementia-related processes. Thus poor sleep appears to potentially be a result of Alzheimer's and a risk factor for the disease. Dr. Wu's team has confirmed these findings using a genetically engineered fruit fly model. They observed flies with beta-amyloid in their brains exhibit reduced and fragmented sleep. In addition, sleep deprivation at night (but not during the day) further increases the insects' beta-amyloid levels.
For their current grant, Dr. Wu and colleagues will use their fly model to identify biological mechanisms underlying the relationship between beta-amyloid and poor sleep. First, they will determine if promoting sleep in their insects helps reduce beta-amyloid levels and improve memory function. Then the team will assess whether increasing or decreasing sleep has an effect on a function called autophagy, or the controlled elimination of unwanted substances in the brain. Loss of autophagic functions has been shown to boost the production of dementia-related beta-amyloid. The results of Dr. Wu's work could identify the utility and potential benefit of altered sleep, a modifiable disorder, as a target for Alzheimer's therapies.