Washington University in St. Louis (WU)
Tau dysfunction is implicated in many neurodegenerative diseases, including Alzheimer’s disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and Pick’s disease. Most of these diseases are characterized by tau protein aggregation and are termed tauopathies. In these diseases, tau is affected at the molecular (splicing), protein (hyperphosphorylation, cleavage, aggregation), and cellular (secretion) levels. Thus, defining the molecular mechanisms underlying tauopathies require unraveling the complexities of the MAPT gene that encodes the tau protein, tau protein dysfunction within the cell, and the cell-cell interactions that produce pathology in the human brain. We use traditional immortalize and human induced pluripotent stem cell-derived neuron and astrocytes to define the molecular and cellular mechanisms underlying tauopathies.