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2012 Grants - Marchetti
Learning From Epilepsy to Understand Alzheimer's Disease
Cristina Marchetti, Ph.D.
European Brain Research Institute
2012 New Investigator Research Grant
Scientists have long thought that epileptic seizures were a complication of Alzheimer's disease. But recent studies have found that seizures may play a key role in activating disease progression. Specifically, accumulations of the protein fragment beta-amyloid, a key suspect in Alzheimer's, appear to initiate epileptic seizures. These seizures, in turn, may lead to further increases in brain beta-amyloid levels—creating a "vicious cycle" that can hinder brain cell communication and cause memory loss. Though the exact mechanisms by which seizures affect cognition are unknown, evidence suggests that the activity of "channels" (or molecular pathways) through which neurons send electrical communication signals becomes altered. These alterations may lead to a toxic process called excitotoxicity, in which nerve cells become overstimulated and damaged. Excitotoxicity is known to promote both seizures and cognitive decline.
Cristina Marchetti, Ph.D., and colleagues will study how changes in neuronal channel activity in the hippocampus may lead to excitotoxicity, brain seizures and cognitive loss. The hippocampus brain region is important for learning and memory, and it tends to be affected early in Alzheimer's disease. For their project, the researchers will use mice genetically engineered to develop Alzheimer's-like symptoms. Electrical activity in these animals' hippocampi will be examined to detect any abnormalities in neuronal signaling. The investigators will also treat their mice with compounds that either promote or inhibit epileptic seizures. These treatments may reveal whether the animals' altered neuronal signaling makes them more vulnerable to seizure-related cognitive decline. The results of Dr. Marchetti's work could help clarify—step by step—how neuronal signaling changes can lead to memory loss in dementia.