Tau is a microtubule-associated protein (MAP), the main function of which is to stabilize microtubules implicated in axonal transport and axon structure1. In pathological conditions, and for reasons that remain to be elucidated, tau detaches from microtubules and assembles into paired helical filaments (PHF) to form intracellular inclusions2,3. In physiological conditions, tau is considered to be an unfolded protein mainly associated to microtubules. However, post-translational modifications, such as hyperphosphorylation and conformational changes, promote the transition towards pathological forms of tau. Several neurodegenerative diseases are characterized by the progressive accumulation of modified tau, including Alzheimer’s disease and frontotemporal dementia and FTDP-174. In FTDP-17, several autosomal dominant missense mutations identified in the tau gene demonstrate that the modification of tau protein can cause neurodegeneration and dementia5. In Alzheimer’s disease, tau pathology is associated with its hyperphosphorylation, conformational changes and deposition in NFT, in the absence of any mutation in the tau gene. However, the development of the tau pathology correlates with neuronal loss and progressive cognitive deficits. This indicates that the post-translational modifications of normal tau confer a crucial role for this protein in neuronal dysfunction and neurodegeneration6–8.