2005 Investigator-Initiated Research Grant

Though it is well established that a mutation in one of three genes is responsible for rare, inherited forms of Alzheimer’s disease, what causes the vast majority of Alzheimer cases is still not well understood. However, the inherited forms of the disease do provide some important clues.

Two of the three genes linked to the inherited disease provide instructions for making proteins called presenilin-1 and presenilin-2. Many researchers believe that proteins that interact with the presenilins might play a role in Alzheimer’s disease.

Recently, Gabrielle L. Boulianne, Ph.D., and colleagues found that some proteins which regulate cellular levels of calcium can also bind to presenilin-1. Because small changes in calcium levels can have profound effects on neurons, even leading to the death of cells, these calcium-binding proteins could very likely be involved in Alzheimer’s disease process.

To investigate this further, the researchers plan to examine the interaction between these proteins and the presenilins. They will determine if the presenilin mutations that cause familial forms of the disease also affect levels of calcium in neurons and if this change might be sufficient to cause the neuronal damage found in Alzheimer brains. This study will help scientists understand the biological problems that lead to the disease and might also lead to the identification of new targets for drug development.