Detection of a Cdc2-related kinase associated with Alzheimer paired helical filaments

By immunocytochemical staining and Western blotting, we detected a Cdc2-related kinase in human brains. The kinase is recognized by antibodies against the carboxyl and the amino termini of p34Cdc2 but is not recognized by antibodies against the PSTAIRE motif. It is slightly smaller than p34Cdc2 in molecular mass (approximately 33 kd). This 33-kd Cdc2-related kinase is present in intracellular neurofibrillary tangles in neurons of elderly humans and in Alzheimer's disease, and it is associated with paired helical filaments (PHF) from Alzheimer's disease brains. Unlike the antibodies to the carboxyl and amino termini of p34Cdc2, antibodies to an abundant brain Cdc2-related kinase PSSLARE/Cdk5 did not immunolabel Alzheimer's disease neurofibrillary lesions. PHF preparations were demonstrated to contain kinases capable of phosphorylating histone H1, PHF-Tau, and a synthetic peptide (VAVVRTPPKSPSSAK). By virtue of its physical association with PHF, the 33-kd Cdc2-related kinase may play a role in transforming normal Tau proteins to PHF-Tau characteristic of Alzheimer's disease.