ATTENUATED PROTEIN-KINASE-C ACTIVITY AND TRANSLOCATION IN ALZHEIMERS-DISEASE BRAIN

Protein kinase C (PKC) activity and its redistribution were determined in postmortem Alzheimer's disease (AD) and age-matched control brains . Cytosolic and membrane-associated PKC activities were lower in front al and temporal cortices and hippocampi of AD brains. Increased concen trations of phosphatidyl-L-serine, Ca2+ or phorbol 12-myristate, 13-ac etate only weakly increased enzyme activity in AD tissues. Redistribut ion of cytosolic PKC to the membranous fraction was elicited in contro l brain slices by 162 nM PMA in the presence of K+ (65 mM). This redis tribution of the enzyme was markedly reduced in AD brain slices. In co ntrast, the immunoreactivity of the alpha- and gamma-PKC isozymes were elevated in cortical tissue from AD subjects. No changes were noted i n beta-PKC immunoreactivity. These results suggest that the reduced PK C activity and the attenuated translocation of the enzyme in AD brain tissue may be attributed to down regulation of PKC or to alteration in PKC protein. The increase in PKC immunoreactivity may be a reflection of an altered susceptibility to proteolysis or a compensatory respons e secondary to the loss in enzyme activity.