Besides the fact that Braak and collaborators showed that AD-related pathology proceeds in strictly defined stages, based on the notion that NFT evolve from an accumulation of abnormal tau without PHF formation (described as the “pre-tangle” stage, [123]) they also proposed that abnormal phosphorylation is a crucial step leading to the formation of both soluble and insoluble tau filaments [124], that neuronal damage in AD actually starts many years before any clinical symptoms and signs and that, unlike Aβ, the distribution of tau pathology is associated with the clinical progression of AD. Here, MAPT is linked to Alzheimer disease.