Testing For Calcium Dysregulation In A New AD Model

Thomas Jongens, PhD The Trustees of the University of Pennsylvania


One hypothesis, put forth by several investigators, is that dysregulation of intracellular calcium is an early or central cause of at least some of the symptoms of Alzheimer's disease. In the experiments outlined in this proposal we will determine if the misregulation of intracellular calcium levels is linked to the age of onset of cognitive deficits that we observe in a new Drosophila (fruit fly) model for Alzheimer's disease that is based on loss of presenilin activity.

Project Details

One way that people get Alzheimer's disease is a by having mutations in the presenilin gene. We have made a fruit fly model of Alzheimer's that has a mutant form of presenilin. Because of their short life-spans and well characterized genome, fruit flies are often used by biologist to study genetics. Interestingly we have found that as these mutant flies age they suffer from a loss of learning and memory, much like Alzheimer's patients. Previous studies suggest that mutation of the presenilin gene results in higher levels of calcium in cells and this might be the cause of some of the symptoms of Alzheimer's disease. We have found that if we treat our Alzheimer's model flies with drugs that should reduce the levels of calcium in cells, we can prevent the loss of learning and memory that occurs with aging in these flies. Our research will look at two items:: if, in fact, calcium levels are higher in the cells of our fly model and if the drug treatments that prevent the loss of learning and memory also bring the calcium levels back to normal. If we can show this, our results will indicate that drug treatments that can reduce calcium levels in cells should be explored as a possible treatment for Alzheimer's disease.