Tau Immunotherapy Modulates Both Pathological Tau and Upstream Amyloid Pathology in an Alzheimer's Disease Mouse Model

In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid beta protein (A beta). However, the relationship between these two proteins and memory loss is unclear. In this study, we evaluated the specific removal of pathological tau oligomers in aged Tg2576 mice by passive immunotherapy using tau oligomer-specific monoclonal antibody. Removal of tau oligomers reversed memory deficits and accelerated plaque deposition in the brain. Surprisingly, A beta*56 levels decreased, suggesting a link between tau and A beta oligomers in the promotion of cognitive decline. The results suggest that tau oligomerization is not only a consequence of A beta pathology but also a critical mediator of the toxic effects observed afterward in AD. Overall, these findings support the potential of tau oligomers as a therapeutic target for AD.