O5‐04‐05: A NEW THERAPEUTIC STRATEGY FOR TAUOPATHIES: DISCOVERY OF HIGHLY POTENT BRAIN PENETRANT PROTAC TM DEGRADER MOLECULES THAT TARGET PATHOLOGIC TAU PROTEIN SPECIES

tissue, but not in seeding incompetent tau from control or AD brain tissue. Immunoprecipitation of ubiquitinated proteins resulted in a seeding competent preparation that was highly abundant in tau. Conclusions: Our data show that charge neutralizing modifications are present in the core region of AD tau. Based on these results and the known cryo electron-microscopy structure of tau filaments, we propose a model where accumulation of charge neutralizing PTMs promotes the formation of tau aggregates.