An emerging view is that neurofibrillary tangles (NFT) themselves are not the true toxic entity in Alzheimer`s (AD) and other tauopathies; rather, aggregates of a size intermediate between monomers and NFT- so-called tau oligomers- are pathogenic. Recently my laboratory developed novel polyclonal and monoclonal antibodies that recognize specifically oligomeric forms of tau. These novel reagents and methodologies we have developed should enable us for the first time to systematically assess the role of tau oligomers in AD and other tauopathies in patients and in animal models. The final aim of the proposal is to target tau oligomers in mouse models via a vaccine approach which I believe could yield a disease-modifying therapy for AD in the next 10-15 years.