Alzheimer's disease (AD) was first described more than a hundred years ago. With longer life expectancy, its incidence has increased dramatically and current forecasts speak in terms of a doubling of the number of persons affected every 20 years.¹  AD is the most frequently encountered form of dementia (about 70% of cases of dementia). The definitive diagnosis of AD is based on the observation of characteristic brain lesions, usually found during a post-mortem examination: senile plaques and neurofibrillary tangles.

Neurofibrillary degeneration consists of the intraneuronal accumulation of proteinaceous fibrils forming flame-shaped neurons into paired helical filaments (PHF) (for reviews see Buee et al.,²  Sergeant et al.³ ). The major antigen of PHF was shown to correspond to Tau protein, which is phosphorylated. Tau is a neuronal protein essentially located within the axonal compartment. Its structure makes it essential for the organization, stabilization and dynamics of microtubules,^2,3  but recent data also emphasize that Tau has other important neuronal functions at the dendritic and nuclear levels.^4–6  The physiologic and pathologic functions of Tau are also regulated by post-translational modifications such as phosphorylation. In AD and related disorders, aggregated Tau proteins are always found hyperphosphorylated. These changes in phosphorylation may affect a number of Tau functions and facilitate Tau aggregation.^2,3  In AD, Tau pathology spreads to the basal forebrain and several cortical areas in an anatomically defined pattern⁷  along neuronal projections defining the Braak stages of Tau pathology.⁸  These stages are well correlated to the severity of dementia.^9,10  This supports the instrumental role of Tau pathology in cognitive alterations.