Peter Dodd, Ph.D.
University of Queensland
Brisbane, Queensland, Australia

2003 Investigator-Initiated Research Grant

One of the mysteries of Alzheimer’s disease is the fact that brain cells in certain areas of the brain are destroyed, while cells in other areas are apparently unaffected. Because many critical molecules are not distributed uniformly across the brain, one possibility is that the biochemical environment in certain areas favors or even promotes the destructive processes of the disease.

One molecule of particular interest is the messenger chemical glutamate, which plays a normal role in cell-to-cell signaling in many parts of the brain. However, glutamate has also been implicated in the death of nerve cells under certain conditions.

Peter Dodd, PhD, and colleagues hypothesize that regional variations in the way glutamate is regulated could make some brain areas more vulnerable to glutamate-induced cell damage in Alzheimer’s disease. In this study, they are going to map the distributions and concentrations of a group of proteins called “transporters” that help regulate the activity of glutamate. In postmortem tissue from the brains of people with and without Alzheimer’s, they will compare the distributions of glutamate transporters with distributions of the abnormal proteins beta-amyloid and tau, the prime suspects in Alzheimer’s. Finding that local variations in glutamate transporters underlie susceptibility to Alzheimer’s would suggest that preventing glutamate toxicity could be a potential therapy.