CYTOSOL PROTEIN-KINASE-C DOWN-REGULATION IN FIBROBLASTS FROM ALZHEIMERS-DISEASE PATIENTS

We attempted to determine whether changes in protein kinase C (PKC) ac tivity in Alzheimer's disease (AD) brains are also present in cultured skin fibroblasts from living patients. Biopsies collected from should er skin were transferred to culture plates with an appropriate growth medium, and histone-directed PKC activity as well as phorbol ester bin ding were individually determined in soluble and particulate fractions prepared from AD and non-AD fibroblast cell lines. Binding experiment s indicated that PKC was unevenly distributed between cytosol (78%) an d particulate (22%). The B(max) values for phorbol ester binding in so luble and particulate fractions were similar in AD and non-AD patients . K(d) values in the cytosol were 94% higher in AD patients, indicatin g lower affinity of the enzyme for the ligand. Accordingly, the solubl e PKC activity was 30% lower in AD patients. The data suggest that the changes in PKC phosphorylating activity represent a diffuse cellular defect in AD and are not confined to the brain. The alterations of the enzyme may participate in the disregulation in processing of beta-amy loid precursor protein in AD.