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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.

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