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2015 Grants - Gräff
Neuronal Activity as a Trigger for Alzheimer’s Disease: A Cell Type-Specific Investigation
Johannes Gräff, Ph.D.
Ecole Polytechnique Fédérale de Lausanne (EPFL)
2015 New Investigator Research Grant
How does abnormal activity in certain nerve cells contribute to the development of Alzheimer’s disease?
Because Alzheimer’s disease is a progressive disorder, much dementia research has focused on identifying brain changes that occur in the earliest disease stages. A greater understanding of these changes could lead to the development of therapies that slow the disease’s progress before memory loss and other clinical symptoms arise. According to recent studies, certain nerve cells become excessively active early in the disease process. Such prolonged activity may damage the nerve cells and prevent them from communicating with one another, leading to problems with memory and other cognitive functions.
Johannes Gräff, Ph.D., and colleagues have developed a new genetically-engineered mouse to specifically study these types of brain changes. This mouse has been engineered to develop Alzheimer’s-like brain changes and also contain a compound that can bind to and “highlight” specific nerve cells that become abnormally active.
For their current studies, Dr. Gräff and colleagues will use their genetically-engineered mice to identify which types of nerve cells display excessive activity early in the disease process. They will then isolate these nerve cells to study their molecular and genetic features in detail. The researchers will also chemically “deactivate” this specific group of nerve cells, in order to determine if this “quieting” can reduce Alzheimer’s-associated brain changes and improve cognitive function.
Dr. Gräff’s effort could improve our understanding of how abnormal nerve cell activity may trigger the molecular and cellular changes that contribute to Alzheimer’s disease. These findings could also promote the development of novel strategies for diagnosing and possibly treating the disease at an early stage.