Alzheimers disease is accompanied by the accumulation of senile plaques composed of insoluble amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs).Aberrant NFTs are predominantly comprised of twisted double-helical ribbons referred to as paired helical filaments (PHFs).These filaments are made up of the Tau protein.The essential amyloid core motifs responsible for the aggregation of the Tau protein are known as PHF6* and PHF6, and are found, respectively, at the beginning of the R2 and R3 microtubule-binding repeat domains.PHF6 and PHF6* are hexapeptide sequences that are essential for the initiation of aggregation and which can indeed form fibrils themselves.Understanding the underlying molecular mechanism of the aggregation of the Tau protein is essential for the rational design of small molecular inhibitors of this deleterious process.