Peptide Imaging Agents Specific for Tau Aggregates

Project Summary

As the first step of our investigation, we will generate small probes that recognize different forms of tau protein aggregates. Our approach is to use a small and stable scaffold that will be mutated to generate large libraries of variants with sequence differences in the binding loops. We will introduce different functional groups (amino acids) at several sites in the binding loops that have a wide range of properties, including amino acids with positive and negative charge as well as those with hydrophobic (water hating) or hydrophilic (water loving) groups. Next, we will use high-throughput screening methods to sort these large libraries in order to select rare variants (ie, the “needles in the haystack”) that selectively recognize toxic forms of the tau protein that are associated with Alzheimer’s disease (AD). Finally, we will evaluate these novel probes as imaging agents for detecting toxic tau protein particles in the brains of mice used as models of AD. Our long-term goal is to translate this technology to humans for early and accurate detection of Alzheimer’s disease.