DETECTION OF A CDC2-RELATED KINASE ASSOCIATED WITH ALZHEIMER PAIRED HELICAL FILAMENTS

By immunocytochemical staining and Western blotting, we detected a Cdc 2-related kinase in human brains, The kinase is recognized by antibodi es against the carboxyl and the amino ter-mini of p34(Cdc2) bat is not recognized by antibodies against the PSTAIRE motif. It is slightly sm aller than p34(Cdc2) in molecular mass (approximately 33 kd). This 33- kd Cdc2-related kinase is present in intracellular neurofibrillary, ta ngles in neurons of elderly humans and in Alzheimer's disease, and it is associated with paired helical filaments (PHF) from Alzheimer's dis ease brains. Unlike the antibodies to the carboxyl and amino termini o f p34(Cdc2), antibodies to an abundant brain Cdc2-related kinase PSSLA RE/Cdk5 did not immunolabel Alzheimer's disease neurofibrillary lesion s. PHF preparations were demonstrated to contain kinases capable of ph osphorylating histone HI, PHF-Tau, and a synthetic peptide (VAVVRTPPKS PSSAK). By virtue of its physical association with PHF the 33-kd Cdc2- related kinase ma play a role in transforming normal Tau proteins to P HF-Tau characteristic of Alzheimer's disease.