The prion model makes important predictions regarding novel therapeutic approaches in neurodegenerative diseases. We have already helped introduce a new therapeutic antibody to the clinic that blocks trans-cellular propagation. We anticipate that there are multiple modes by which an antibody can prevent neuropathology in protein amyloid diseases, and that elucidation of the mechanisms will lead to next-generation agents with improved efficacy. Our knowledge about the mechanisms underlying tau prion entry into cells has also sparked several drug development efforts. We are creating compounds to interfere with tau aggregate binding to the cell surface. Additional studies use molecular genetics to identify modifiers of cellular seeding and propagation that we hope will pinpoint key enzymatic targets for drug discovery. New approaches to diagnostics center on creating super-sensitive detection methods for tau prions, and at the same time determining their structural characteristics. This will depend on vigorous technological advancement and method development. For example, we have developed a cell-based assay that enables detection and quantification of tau prions in brain far in advance of any neuropathology, and which we are now adapting to define underlying tau prion strain composition. We are collaborating with other members of the Center for Alzheimer’s and Neurodegenerative Diseases to develop new ways to detect and characterize pathogenic tau prion conformers in peripheral fluids and brain. Ultimately we envision bringing these approaches to the clinic to predict disease prior to symptom onset.