A Newly Discovered Version of Toxic Tau as a Therapeutic Target in Alzheimer's Disease

Project Summary

Tau is a key protein in Alzheimer's disease, but that protein can take many different forms depending on its content. Daniel C. Lee, PhD, and his colleagues have discovered a new form of tau, one related to changes in the protein's building blocks. The changes involve swapping out the amino acid arginine for the amino acid citrulline at several spots on the protein. The resulting "citrullinated tau"" may be an especially toxic version of tau. 

The discovery presents citrullinated tau as a potential target for therapies in Alzheimer's disease. Dr. Lee and his colleagues plan to assess two therapeutic approaches that target tau citrullination. 

One approach will deploy antibodies that might inhibit the process of swapping the amino acids, so the tau never becomes citrullinated. The group has developed a toolkit of 11 antibodies that cover most of the sites where the amino acid swapping takes place on tau. The other candidate therapy is a vaccine against citrullinated tau. 

The team will test both potential therapies in lab models of Alzheimer's disease. Dr. Lee and his coworkers will compare the effects of the two approaches on disease progression and cognitive decline, opening up a new area of research in Alzheimer's disease.