Live Imaging of Pathological Tau Protein and Tau Antibodies in a Neuron-Like Cellular Model.
Several tau antibody therapies are now in clinical trials and numerous other tau antibodies are in various stages of preclinical development to treat Alzheimer's disease and related tauopathies. This involves long-term studies in mouse models that are necessary but time consuming and typically provide only a limited mechanistic understanding of how the antibodies work and why some are not effective. Live cellular imaging with fluorescently tagged pathological tau proteins and tau antibodies provides a valuable insight into their dynamic interaction outside or within the cell. Furthermore, this acute technique may have predictive validity to assess the potential efficacy of different tau antibodies in neutralizing and/or clearing tau aggregates, and can likely be applied to other amyloid diseases. Overall, it should facilitate identifying candidate antibodies for more detailed long-term validation. Due to the human origin of the model, it may be particularly useful to characterize humanized antibodies that utilize receptor-mediated uptake to reach their intracellular target.