Animal Models of Neuropathology

Animal models are vital to test our hypotheses about fundamental events in pathogenesis, including mechanisms, new therapies, and diagnostic strategies. We seek to test ideas that derive from fundamental studies using biochemistry and cell biology, in anticipation of translating these ideas to patients. We maintain an infrastructure dedicated to rapid and unbiased analysis of neuropathology.

To induce highly specific and predictable patterns of neuropathology, we have developed an inoculation model of tau prion activity. This is based on stereotactic injection into transgenic mice of different tau prion strains that induce spreading pathology within weeks. Since we can purify tau prion strains in vitro, this allows us to directly test how their characteristics define cell vulnerability and rate of spread within the brain. We are also in an excellent position to test the role of modifier genes in the pathogenic process, without having to wait many months for the development of neuropathology.

We are also using mouse models to develop diagnostic and therapeutic methods. We used mouse models to test a therapeutic antibody that is now in early clinical trials. We are also using mouse models to develop blood-based and imaging biomarkers of disease. Our mouse models thus provide a vital extension of our cell and molecular studies.