Dynamic assessment of tau immunotherapies in the brains of live animals by two-photon imaging

Abstract Our original findings, showing the effectiveness of active and passive tau immunizations in mouse models, have now been confirmed and extended by many groups, with several clinical trials underway in Alzheimer's disease and progressive supranuclear palsy. Here, we report on a unique and sensitive two-photon imaging approach to concurrently study the dynamics of brain and neuronal uptake and clearance of tau antibodies as well as the acute removal of their pathological target in live animals. This in vivo technique is more sensitive to detect clearance of pathological tau protein than western blot tau analysis of brain tissue. In addition to providing an insight into the mechanisms involved, it allows for an efficient in vivo assessment of the therapeutic potential of tau antibodies, and may be applied to related protein misfolding diseases.