LRP and Abeta Generation: Role of Cytoplasmic Domains

Project Summary

Recently, several laboratories, including Dr. Pietrzik's, have suggested that a molecule called LRP contributes to the cause of Alzheimer's disease. LRP is a member of the family of lipid receptors. Dr. Dudley Strickland's laboratory (under a BrightFocus grant) reported earlier this year that LRP influences how much amyloid beta is made by cells, and proposed that APP and LRP associate outside of cells to influence amyloid beta production. Dr. Pietrzik's preliminary studies suggest that LRP influences APP and amyloid beta generation intracellularly. He is now testing the hypothesis that the cytoplasmic domains (intracellular parts) of APP and LRP are very important for these two molecules. He will measure the amount of amyloid beta made by cells that have been engineered to produce only shorter intracellular APP and LRP molecules. He is also studying other ways that LRP influences APP to give a more complete picture of how LRP is responsible for amyloid beta production. It is hoped that this work will lead to fundamental knowledge about the causes of AD and further the development of drugs to reduce amyloid beta production. Dr. Pietrzik is also the recipient of an ADR Pilot Program Award.