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2016 Grants - Jacobson
Tau and Orexin Interactions in Sleep and Cognition in Alzheimer’s Disease
Laura H. Jacobson, Ph.D.
Florey Institute of Neuroscience and Mental Health
2016 New Investigator Research Grant
Can abnormal tau protein promote Alzheimer’s disease by disrupting the sleep cycle?
Healthy sleep has been shown to promote brain health including memory formation and enhancing the ability of nerve cells to communicate with one another. People with early-stage Alzheimer’s disease often tend to experience sleep problems. Taken together these findings suggest that improving sleep may help slow the progression of Alzheimer’s. Most current sleep medications, however, are not useful for improving brain health, as they can promote disruptions in memory and other negative side effects.
Recent studies have found that brain levels of orexin, a protein involved in the sleep cycle, become abnormal in Alzheimer’s. Studies have also shown that orexin levels may be affected by abnormal tau, a protein that accumulates into tau tangles, a hallmark of Alzheimer’s disease. More research is needed to better understand the interaction of tau and orexin in the brain and how it affects sleep. If this interaction plays a role in the development of Alzheimer’s, then the orexin pathway may be a promising target for drug therapies.
Laura H. Jacobson, Ph.D., and colleagues will study how abnormal tau and orexin interact to promote sleep disruptions in early-stage Alzheimer’s disease. This effort will involve mice genetically engineered to have either no tau or unusually high levels of abnormal tau in the brain. The researchers will assess how different levels of tau affect the level of orexin in the brain. They will also examine the animals’ sleep patterns and brain function. Lastly, they will examine whether drugs that regulate orexin activity can alter tau levels, sleep function and cognition in the mice.
This research could shed new light on the molecular mechanisms that may link sleep problems and Alzheimer’s disease and help clarify whether sleep problems precede Alzheimer’s, or are an effect of the advancing disease. Ultimately, the results of this work could lead to the development of novel therapies that not only improve sleep quality but may also prevent or slow the progression of Alzheimer’s disease.