2012 Grants - Scharfman

Circuit-Based Strategies in Alzheimer's Disease and Epilepsy

2012 Neuronal Hyperexcitability in Seizures and Alzheimer's Disease Research Grant

The brain contains many different regions, some of which are more vulnerable to damage than others. Two regions of the brain that are especially vulnerable to damage during the early stages of Alzheimer's disease are known as the entorhinal cortex and the hippocampus. Nerve signals are sent between these two regions along a group of nerve fibers known as the perforant path, which is also vulnerable. The same brain regions and pathways are also known to be involved in seizures in people who have epilepsy.

Helen Scharfman, Ph.D., and colleagues have been studying the perforant path and its connection to the hippocampus in mice that were genetically engineered to exhibit Alzheimer's-like characteristics in the brain. The researchers observed that stimulation of the perforant path causes abnormally high activity of a group of nerve cells in the hippocampus, known as granule cells. They suspect that abnormal activity of granule cells may be an early step in the process of neurodegeneration in Alzheimer's disease.

Several drugs that prevent seizures in people who have epilepsy reduce the excitability of hippocampal granule cells. Therefore, Dr. Scharfman and colleagues have proposed to study whether these drugs can reduce or prevent the abnormal activity that precedes damage in the brain regions that are vulnerable in Alzheimer's disease. Some of these drugs have also been shown to improve memory in animal models of Alzheimer's disease. These studies will test an important idea about early nerve damage in Alzheimer's disease and potentially identify drugs to prevent or reduce that damage.