Defining the molecular basis for inhibiting LRP1-mediated cellular propagation of pathogenic tau

2020 Pilot Project Read More


Principal Investigator: Thomas Brett (WashU Medicine)
Collaborator: Gaya Amarasinghe (WashU Pathology & Immunology)


Cell-to-cell propagation of pathogenic tau is a major mechanism that contributes to spread of neurotoxic tau and neuronal death in Alzheimer’s disease. The low-density lipoprotein receptor-related protein 1 (LRP1) is the major receptor mediating uptake of tau into neurons and, thus, potentially contributing to pathogenic tau propagation throughout the brain. We have identified a viral glycoprotein that can bind LRP1 with high affinity and potently block tau engagement. In this project, we will structural and biochemical methods to characterize LRP1-tau interactions and investigate how the viral glycoprotein can block LRP1-mediated tau spreading. We also expect our studies to develop a framework to design new therapies to inhibit the propagation of pathogenic tau in AD and other dementias.


Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Thomas Brett