Gene therapy for Alzheimer's disease using virally delivered Aß variants

Our research focuses on the pathogenesis of Alzheimer’s disease. Broadly speaking, we want to understand factors that influence disease risk and dictate the stereotyped loss of neural circuits needed for memory. More specifically, we want to understand how aging increases the likelihood of dementia, how genetics may influence this risk, and how specific brain areas are selectively affected.

Our laboratory uses transgenic mice as a model system that can be engineered to reproduce focused aspects of the disease. These models allow us to test cellular and molecular hypotheses about causes and consequences of disease pathology, and to define how interactions between genes, environment, and aging determine resilience or risk.

We are currently pursuing three avenues of study. One project explores the genetic basis of cognitive reserve by engineering mice to express a gene variant associated with preserved cognition in patients with Alzheimer's neuropathology. Complementary studies examine how brain aging contributes to Alzheimer's risk using mice designed to stop time through exogenous control of amyloid onset. Finally, we are investigating the basis for progressive neuronal vulnerability in Alzheimer's using mice created to test whether circuit function contributes to disease susceptibility. Our hope is that mice and men share sufficient similarities in genetic architecture, basic physiology, and neuronal circuitry to gain insight from one useful in understanding the other.