The pathologic deposition of tau filaments mainly composed of hyperphosphorylated forms of the protein appears to correlate with the symptoms observed in FTDP and Alzheimer’s disease6–8. In the molecular processes leading to the tau pathology, the dissociation of the tau protein from the microtubules appears as a primary event, whereas tau hyperphosphorylation may prevent the re-association of the protein with the microtubule network. The amount of tau, with respect to the available sites for microtubule binding, determines the level of free tau protein in the cytosol, which is the starting point towards the formation of pathological tau, either hyperphosphorylated or misfolded into PHF, or both. Therefore, tau overexpression appears as a rational approach to promote the deposition of different forms of tau and assay how they contribute to pathology.