Application of synthetic phospho- and unphospho- peptides to identify phosphorylation sites in a subregion of the tau molecule, which is modified in Alzheimer's disease.

Phospho- and unphospho- peptides were used to define the essential sequence for a tau epitope, which is recognized by Tau-1 antibody and phosphorylated in Alzheimer's disease (AD). The epitope was mapped within the amino acid residues 192-199 of tau and was phosphorylated by the p34cdc2/p58cyclin A proline directed kinase (PDPK), but not by purified mitogen activated protein kinase (p42mapk). Addition of phosphate to the last serine of the epitope was the most effective in abolishing the reactivity of the epitope to Tau-1 antibody. Our results suggest that one and possibly more members of the PDPK family may play a role in the pathogenesis of AD.