Paired Helical Filaments (PHF) accumulate in the degenerating neurons from the associative cortical brain areas during Alzheimer's disease. They are composed of a triplet of hyperphosphorylated microtubule-associated protein Tau, called Tau 55, 64, 69 or PHF-Tau. The distribution of PHF-Tau in the different brain areas corroborates neuropathological observations and specifies that: the entorhinal cortex and hippocampus are vulnerable regions specifically affected by Alzheimer-type neurofibrillary degeneration during aging, the temporal cortex is already affected at the very first stage of clinical manifestations, almost the whole brain is concerned by neurofibrillary degeneration at the end-stages of the disease. Tau-PHF are also observed in the cortical areas from Parkinson patients with dementia, and more especially in the prefrontal cortex. Tau pathology for Progressive Supranuclear Palsy is significantly different, with a doublet of pathological Tau, namely Tau 64 and 69, in almost all cortical and subcortical areas. Therefore, the presence of pathological Tau proteins in several associative cortical areas is always associated with severe intellectual impairment. Finally, PHF-Tau are powerful biochemical markers of the degenerating process which could be used for setting up an early biological diagnosis test of Alzheimer's disease based upon the immunodetection of PHF antigens in the CSF, as well as for developing experimental models of neurodegeneration.