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2010 Grants - Pierce-Shimomura
Mechanisms of APP-Induced Death of Cholinergic Neurons in C. Elegans
Jonathan Pierce-Shimomura, Ph.D.
University of Texas at Austin
2010 New Investigator Research Grant
The protein fragment beta-amyloid, a key suspect in Alzheimer's disease, is clipped from a larger molecule called amyloid precursor protein. Beta-amyloid accumulates into clumps called plaques, which are a hallmark of the Alzheimer brain. Yet recent studies have found that amyloid plaques might not be as toxic to the brain as previously thought. Some researchers have begun exploring the potential role of APP itself in Alzheimer's.
In preliminary research, Jonathan Pierce-Shimomura, Ph.D. and colleagues have been studying how overexpression of APP may lead to brain disease in roundworms. They have found that this overexpression results in age-related damage to specific cholinergic neurons. These neurons are closely associated with learning and memory in humans, and they are the among the first brain cells affected by Alzheimer pathology.
For their proposed grant, the researchers plan to study in detail how APP overexpression damages roundworm cholinergic neurons. The worms' transparent bodies make the study of neuronal degeneration relatively easy and inexpensive. Dr. Pierce-Shimomura and colleagues will determine which regions of worm APP are specifically associated with neuronal damage. They will also identify where on the cholinergic neuron APP exerts its toxicity. In addition, they will search for genetic mutations that may be involved in APP-induced neuronal damage and death.
The findings of this study may shed new light on the toxic role of APP in Alzheimer's disease. It may also promote further Alzheimer studies using the cost-effective roundworm models.