Harnessing Microglia to Internalize and Degrade Tau 

Principal Investigator: Dr. Sarah Hopp, Glenn Biggs Institute for Neurodegenerative Disorders, The University of Texas Health Science Center, San Antonio, TX

Misfolded tau is found floating around outside of cells in the extracellular space of the brain, where it is harmful to neurons and other cells. Additionally, extracellular misfolded tau can also enter brain cells and cause normally folded tau within those cells to misfold. As tau spreads through the brain, symptoms of PSP and other tauopathies progress. Microglia, the immune cells of the brain, are exceptionally good at cleaning up debris in the extracellular space, including misfolded tau. Our recent research shows that microglia readily internalize and degrade tau, but the specific processes microglia use for that are unknown. We have also recently discovered that microglia that internalize tau are different from microglia that do not. The first goal of our research is to figure out precisely how microglia internalize and degrade tau. The second goal of our research is to figure how tau affects microglia once it is internalized. Overall, we want to identify how we could enhance microglial internalization and degradation of tau to treat PSP and other tauopathies.