QUANTITATIVE-ANALYSIS OF TAU-PROTEIN IN PAIRED HELICAL FILAMENT PREPARATIONS - IMPLICATIONS FOR THE ROLE OF TAN PROTEIN-PHOSPHORYLATION IN PHF ASSEMBLY IN ALZHEIMERS-DISEASE

In Alzheimer's disease, there is a major redistribution of the tan pro tein pool from soluble to PHF-bound forms. PHF-bound tau can be distin guished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation i n the if-II protocol developed in this laboratory. We show that 85% of tau bound in the PHF-like configuration can be recovered in the if-II PHF-fraction. Less than 1% of this material was phosphorylated at the mAb AT8 site in aged clinical controls or in cases with minimal or mi ld dementia. Of tan phosphorylated at the mAb AT8 site, only 12% was f ound to co-sediment with PHFs. These low levels could not be explained by postmortem dephosphorylation. As more than 95% of PHF-tau is not p hosphorylated, even at early stages of pathology, it is misleading to use the terms ''PHF-tau'' and ''phosphorylated tau'' as though they we re synonymous, particularly as this implies a pathogenetic role which phosphorylation need not have.