Active and passive immunotherapy against tau: Effects and potential mechanisms

The aggregation, hyperphosphorylation, and accumulation of the microtubule-associated protein tau is a hallmark for several neurodegenerative diseases, including Alzheimer’s disease. These diseases are known as tauopathies. In tauopathies, the tau protein becomes hyperphosphorylated and forms intracellular neurofibrillary tangles visualized within dystrophic neurites and cell bodies. Evidence suggests that some tau aggregates can become extracellular where they potentially propagate between cells and induce tau pathology in previously unaffected cells. The amount of tau pathology correlates well with the load of neurofibrillary tangles, synaptic loss, and functional decline in humans as well as in transgenic mouse models of tauopathy. Several active and passive immunization studies targeting tau in transgenic mouse models have shown reduced tau pathology, although the mechanism(s) underlying these effects is not clear. In this chapter, we review the recent active and passive immunization strategies targeting tau in mouse models and our understanding of potential mechanisms underlying the effects seen.