Characterization and differential distribution of the three major human protein kinase C isozymes (PKC alpha, PKC beta, and PKC gamma) of the central nervous system in normal and Alzheimer's disease brains

Abstract

Brain kinases may play important roles in normal memory as well as in the pathogenesis of neurodegenerative diseases. However, there is scant information on these enzymes in the human brain. For this reason, we characterized the immunohistochemical localization of protein kinase C (PKC) isozymes in human Alzheimer's disease (AD) and non-AD control brains. Using monoclonal antibodies to PKC alpha, PKC beta, and PKC gamma isozymes, we (a) determined the distribution of each PKC isozyme in eight different brain regions (cerebellum, hippocampus, as well as midfrontal, orbital frontal, motor, occipital, parietal, and temporal cortices) from AD and non-AD control brains and found that these patterns were generally similar to those in the rat brain; (b) showed that there were no significant differences in the normal staining intensity of the monoclonal antibodies in AD and non-AD control brain regions except in the hippocampus; (c) observed striking PKC immunoreactivity in globular and linear profiles in the periphery (corona) of AD senile plaques; and (d) demonstrated that PKC alpha immunoreactivity was enhanced in reactive astrocytes associated with senile plaques and other lesions (embolic infarcts) in both AD and non-AD control brains. The data on the normal distribution of each PKC isozyme were corroborated in quantitative studies of PKC alpha, PKC beta, and PKC gamma protein levels in human postmortem brain regions by Western blotting using our antibodies. We conclude that these three major PKC isozymes can be analyzed directly in postmortem human brain, which is an important first step in understanding the potential role that abnormal phosphorylation might play in the pathogenesis of AD.