Jada Lewis, Ph.D.

Recovery in a Conditional Mouse Model of Tauopathy

Diseases that are characterized by neuronal degeneration and neuronal (or glial) accumulation of the protein tau are termed tauopathies. These diseases include Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We have recently generated and characterized a conditional mouse model of human tauopathy that displays neuronal loss, and show cognitive dysfunction similar to that observed in human tauopathies. We have used these mice to demonstrate that cognitive dysfunction can be recovered, despite preexisting neurofibrillary tangles and neuronal loss. These mice therefore represent a new model in the fight against Alzheimer's disease and other tauopathies; however, more importantly, the ability of the mice to recover cognitive function despite preexisting tauopathy indicates that patients in both early stages and late stages of the disease process may still benefit from therapeutic intervention.

We propose to address the fundamental issue of how the brain can recover function from tauopathy. Our first aim will test the hypothesis that the brain can remodel the neurons or their connections (neuronal remodeling) to recover from tauopathy. Secondly, we will determine if the brain can up-regulate the production of new neurons (neurogenesis) to compensate for the neuronal damage from tauopathies. These studies should help us understand the brain's natural recovery strategies for tauopathy and assist us in identifying potential therapeutic systems that could be used for patient treatments.