Chapter 8 – Tau Proteins

Alzheimer’s disease (AD) is classically defined by the accumulation of abnormal aggregates mainly comprised of two proteins: phosphorylated tau (ptau) and amyloid beta (Aβ). It has been proposed that those aggregates lead to several cellular changes that are translated into neuronal loss and the impoverishment of cognitive functions. Although there is a strong correlation between these protein aggregates and dementia, the exact mechanisms connecting their pathological effects remain poorly understood. Indeed, the role of Aβ deposition as the event that causes the AD pathology is currently under heated debate. In contrast, tau deposits are far more related to clinical dementia. However, during AD development, the dynamic cellular and molecular relationship between tau and Aβ remains under extensive study. Clearly, both proteins are well related to the disease progression and not surprisingly both are currently the main therapeutic targets for new AD treatments. Unfortunately, nothing but moderate success has emerged from a variety of therapeutic strategies targeting either tau or Aβ. One potential explanation for the current failure is that therapeutic interventions are provided at late stages of the disease instead of being administrated at early stages. Taking this hypothesis into account, we will discuss the role of abnormally ptau protein as an early AD marker and discuss the molecular relationships between Aβ and ptau during synaptic activity. Finally, as a proposal that aims to restore normal brain activity, we will briefly discuss a therapeutic strategy that would be based on modifying several tau protein targets by cocktail therapies.