Our research centers on understanding how subtle memory complaints progress to the overwhelming dementia of Alzheimer’s disease. Broadly speaking, we want to identify what triggers the disease, what exacerbates the symptoms, and what can be done to intervene therapeutically. Our lab uses transgenic mice as a model system that can be engineered to reproduce certain aspects of the disease. The models allow us ask directed questions about the underlying biology of Alzheimer’s disease and which treatments may offer maximal benefit.
We are currently focused on two facets of the disease. Most of our studies explore the role of the amyloid precursor protein and its derivative Aß peptide in neuronal dysfunction, subsequent cognitive decline, and potential recovery. Complementary studies are directed at dissecting the specific neuronal circuits involved in the characteristic progression of behavioral symptoms. Ultimately, only human clinical trials will tell us how to cure Alzheimer’s disease and from their success or failure will we truly know what causes the disease, but the mouse models will help us learn how to get there.
Key questions (there are many!)
1. What is the molecular basis for Alzheimer’s disease? How does a small peptide like Aß lead to the devastating cognitive decline of AD? Can we use rare familial cases of early-onset AD to understand how the more common sporadic disease begins?
2. Which neuronal circuits underlie the behavioral progression of AD? Do intraneuronal tangles or extracellular plaques better map the damaged neuronal circuits responsible for each stage of the disease?
3. Will treatments that work early in disease be as effective at later stages, or is there a point at which therapy directed against Aß is no longer effective?
4. How much therapy is enough? If Aß remains an effective target for treatment, will lowering its concentration be adequate for functional recovery or will we need to remove amyloid to attain maximal benefit?