2004 New Investigator Research Grant

Beta-amyloid is a protein fragment that has long been a key suspect in Alzheimer’s disease pathology, but its exact function in disease processes has not been clearly established. Beta-amyloid clumps together in stages with the final stage being structures called amyloid plaques; however, clusters of only a few protein fragments in early stages of aggregation, called oligomers, may be the most toxic form of beta-amyloid.

Previous research has shown that beta-amyloid oligomers may impair cell-to-cell communication at synapses, the tiny “channels” across which brain cells send messenger chemicals. Changhai Cui, Ph.D., and colleagues have observed that beta-amyloid oligomers may disrupt the transfer of glutamate, one of the key messengers in the brain. This disruption could be a primary cause of learning and memory deficits in Alzheimer’s.

There are three types of receptors, or receivers, of glumate messengers, and the investigators have found that beta-amyloid oligomers may change how these receptors function. In this study, researchers will use a variety of laboratory methods to characterize how different-sized oligomers affect the function of the three glutamate receptors and to explore the molecular mechanisms that underlie these changes in function. The findings from this work may suggest therapeutic strategies to correct or lessen dysfunction in cell-to-cell communication and to prevent deficits in learning and memory skills.