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2016 Grants - Du
OSCP Aberration and Synaptic Injury in Alzheimer’s Disease
Heng Du, M.D., Ph.D.
The University of Texas at Dallas
2016 Alzheimer’s Association Research Grant (AARG)
How does beta-amyloid accumulation in the brain damage nerve cell synapses in Alzheimer’s disease?
The accumulation of beta-amyloid protein fragments into “plaques” in the brain is a hallmark of Alzheimer’s disease. Beta-amyloid can interfere with synapses, the specialized structures through which nerve cells communicate. Synaptic damage may hinder nerve cell communication leading to memory loss and other forms of cognitive decline. Like other cells in the body, nerve cells contain small structures called mitochondria that produce energy for the cell. Heng Du, M.D., Ph.D., and colleagues found that in Alzheimer’s-like mice, the mitochondria located near the synapses of nerve cells do not function properly. It is possible that beta-amyloid accumulation impairs synapse function by directly interfering with mitochondria, but the mechanisms require further investigation.
Dr. Du and colleagues hypothesize that beta-amyloid triggers the loss of a protein called oligomycin sensitivity conferring protein (OSCP), which is needed for normal mitochondria function. For their current studies, they will determine if Alzheimer’s-like mice have declining levels of OSCP in the brain as the disease progresses, and examine if this relates to synaptic damage and memory problems. They have also created a novel Alzheimer’s-like mouse model that produces high levels of OSCP in the brain. The researchers hypothesize that restoring OSCP levels in these mice will protect the brain from the harmful effects of beta-amyloid.
This research could shed new light on how beta-amyloid disrupts nerve cell synapses, and may lead to the development of new treatments to preserve mitochondria function in Alzheimer’s disease. Because other types of neurodegenerative diseases, such as Parkinson’s and Lewy body dementia, also show changes in mitochondrial function in the synapse, this work could open up a new area of research in the treatment of many brain disorders.