Alzheimer's disease: phenotypic approaches using disease models and the targeting of tau protein

Introduction: Hyperphosphorylated and aggregated tau protein is the main hallmark of a class of neurodegenerative disorders known as tauopathies. Tau is a microtubule-binding protein which is important for microtubule assembly and stabilization, for proper axonal transport and overall neuronal integrity. However, in tauopathies, tau undergoes aberrant post-translational modifications that fundamentally affect its normal function. The etiology of these devastating diseases is unclear and there is no treatment for these disorders. Areas covered: This review examines the neurobiology of tau, tau post-translational modifications, and tau pathophysiology. Progress regarding the effort to identify and assess novel tau-targeted therapeutic strategies in preclinical studies is also discussed. We performed a search on PubMed of the relevant literature published between 1995 and 2020. Expert opinion: Tau diversity and the lack of clinically available test to diagnose and identify tauopathies are major obstacles; they represent a possible reason for the lack of success of clinical trials. However, given the encouraging advances in PET tau imaging and tau neurobiology, we believe that a more personalized approach could be on the horizon and that this will be key to addressing the heterogeneity of tau pathology.