Understanding Alzheimer's Disease One Mouse at a Time

Our research focuses on the pathogenesis of Alzheimer’s disease. Broadly speaking, we want to identify what initiates the disease, what exacerbates the symptoms, and what can be done to intervene therapeutically. Our laboratory uses transgenic mice as a model system that can be engineered to reproduce certain aspects of the disease. The models allow us to ask directed questions about the underlying biology of Alzheimer’s disease and to examine the relationships between pathology and cognitive impairment. 

We are currently pursuing two avenues of study. One set of experiments explores how the amyloid precursor protein and its derivative Aβ peptide elicit neuronal dysfunction in brain regions critical for learning and memory. Complementary studies are directed at modeling the functional deficits caused by damage to specific neuronal circuits that are compromised early in the disease. 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 mouse models may help to guide the way.

Key Questions

1.  What is the molecular basis for Alzheimer’s disease? How does a small peptide like Aβ lead to the devastating cognitive decline of AD? What accounts for the decade of lag time between the start of Aβ accumulation and the onset of memory complaints?

2.  How does aging contribute to AD? Why does this disease primarily strike late in life?

3.  What makes neurons of the entorhinal cortex particularly vulnerable in AD?  Might loss of these cells contribute to both episodic memory symptoms and spatial disorientation?