In 1906, Alzheimer described the clinical and neuropathological characteristics of the disease that was subsequently named after him. Although the paired helical filament was identified as the major component of the neurofibrillary pathology of Alzheimer's disease in 1963, its molecular composition was only uncovered in the 1980s. In 1988, work at the MRC Laboratory of Molecular Biology in Cambridge (UK) provided direct proof that tau protein is an integral component of the paired helical filament. The paper highlighted here [Goedert M., Wischik C.M., Crowther R.A., Walker J.E. and Klug A. (1988) Cloning and sequencing of a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. USA 85, 4051-4055] also reported the first sequerce of a human tau isoform and paved the way for the identification of the six brain tau isoforms that are expressed by alternative mRNA splicing from a single gene. By the early 1990s, it was clear that tau protein is the major component of the paired helical filament and that the latter is made of all six tau isoforms, each full-length and hyperphosphorylated.