Tau immunotherapies for Alzheimer's disease

Alzheimer's dementia (AD) is the most common form of dementia in the World. Pathologically, it is characterized by extracellular β-amyloid plaques and intraneuronal neurofibrillary tangles (NFTs). The latter is composed of irregular, pathological forms of the tau protein. Currently, FDA-approved symptomatic treatments are limited to the targeting of cholinergic deficits and glutamatergic dysfunctions. However, as understanding of β-amyloid plaques and NFTs expands, these dysfunctional proteins represent potential therapeutic interventions. The present review article evaluates active and passive immunotherapies in clinical development for AD to date and their potential to significantly improve the treatment of AD going forward.

All clinical trials that have targeted β-amyloid to date have produced somewhat disappointing results, leading to a shift in intervention focus to targeting tau protein. A key component in understanding the value of targeting tau in therapeutic paradigms has come from the conceptualization of prion-like pathological spread of tau isoforms from neuron to neuron, and referred to as 'tauons'. Immunotherapies currently under investigation include approaches aiming at preventing pathological tau aggregation, stabilizing microtubules, and blocking of tauons.

A multi-targeted approach that would use biologics targeting tau offers great promise to the development of effective AD therapeutic interventions.