Assessment of protein kinase C isozymes by two-site enzyme immunoassay in human brains and changes in Alzheimer's disease.

Abstract

We assessed the amount of protein kinase C (PKC) in samples from postmortem normal human and Alzheimer's disease (AD) brains by a two-site enzyme immunoassay that quantitatively identified types alpha, beta, and gamma isozymes. In the normal human brain matter, type beta was the main type present, the majority of each isozyme of PKC being present in the membranous fraction of the brain tissues. In AD brains, the amount of type beta PKC was significantly reduced in the membranous fraction of the temporal cortical tissues. The amounts of types alpha and gamma in the membranous fraction and types alpha, beta, and gamma in the cytosolic fraction in AD brains were lower than in the control brains, but the difference was not significant. There was also a significant decrease in the levels of PKC in the membranous fraction of AD brains, as measured by radioactive phorbol ester binding. These results suggest that the type beta PKC isozyme is mainly present in the human temporal cortex and that reduced levels of type beta PKC in the membranous fraction may reflect a biochemical deficit related specifically to the pathogenesis of AD.