Several lines of evidence point to a critical role for specific brain receptors in the pathologic process of Alzheimer's disease (AD) as well as other neurodegenerative diseases. A specific protein known as tau is considered by many to play an important mechanistic role in early AD, however this hypothesis has been exceedingly difficult to test. Major breakthroughs in clinical dementia research and drug development followed from the advent of plaque imaging agents using a medical imaging technique known as positron emission tomography (PET). In such studies, radioactive drug molecules (radiopharmaceuticals) are injected and the distributions of those molecules are measured using a PET camera. However, we still lack a means to identify and track the evolution certain receptors that precede plaque formation, a major barrier to the rapid identification of AD drug treatments that engage and modify these events. Here we propose to develop and implement and evaluate a new tau imaging agent with excellent sensitivity. This work will provide an essential tool for quantitating tau toward development of new AD pharmaceuticals, and potentially to guide dosing and patient selections in the later stage of clinical trials.