Defining early events of Alzheimer’s and other neurodegenerative diseases is an elusive goal to develop biomarkers for subtypes these heterogeneous diseases and develop therapies to mitigate, or even reverse, disease processes.

We investigate the olfactory, or smell-sensing, system of mice and humans since it is vulnerable early pathologic events of neurodegeneration. One major goal is to identify disease-driving events in the early stages of these diseases in humans, before the onset of symptoms—when therapeutic intervention is most likely to be efficacious. The second major goal is to develop a detailed, mechanistic understanding of these early pathogenic events that are modifiable or reversible.

We combine molecular biological, anatomical, cell-based, and behavioral techniques elucidate pathogenic mechanisms driving neurodegenerative disease. We have generated transgenic mouse lines that exhibit propagated neurodegeneration in defined olfactory neuron populations with temporal precision. We have extended this analysis to cultured human neurons and autopsied human brains, such as frontal temporal dementia and ALS. Additionally, we are developing an odor-memory battery in humans that predict the development of Alzheimer’s disease in a asymptomatic individuals. Results from these studies will inform the development of the next generation of olfactory screening tests for Alzheimer’s disease and identify biomarkers and candidate therapies for further study in early stage patients.