Differential involvement of protein kinase C isozymes in Alzheimer's disease.
Decreased levels of protein kinase C (PKC) and a reduction in the in vitro phosphorylation of a Mr 86,000 protein (P86), the major PKC substrate, are biochemical characteristics of brain tissue from patients with Alzheimer's disease (AD) (Cole et al., 1988). In the current study, we utilized antibodies against individual isozymes of PKC to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC(beta II) was lower in particulate fractions prepared from AD hippocampal and cortical tissue than in controls and higher in AD cytosol fractions from the cortex than in controls. Immunohistochemical studies in AD neocortex revealed reduced numbers of anti-PKC(beta II)-immunopositive neurons and diminished staining intensity. In contrast, AD hippocampal neurons in CA3-CA4 were more intensely stained with anti-PKC(beta II) antiserum than were controls. The concentration of PKC(beta I) was lower in particulate fractions prepared from AD hippocampus than in controls and was higher in soluble fractions prepared from AD cortex than in controls. The concentration of PKC(alpha) was lower in AD particulate fractions than in controls in the hippocampus. Immunohistochemistry with PKC(alpha) antiserum revealed moderately intense neuron staining and an intense staining of glial cells in AD neocortex. The concentrations and histochemical distributions of PKC(gamma) were not altered in the disease. PKC immunoreactivity was also found in neuritic plaques. The staining patterns of neuritic plaques with different isoform antibodies varied considerably. Anti-PKC(alpha) faintly stained entire plaques and surrounding glial cells; anti-PKC(beta I) stained dystrophic plaque neurites; and anti-PKC(beta II) stained the amyloid-containing portions of plaques.
Masliah
E
E
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093.
Cole
G
G
Shimohama
S
S
Hansen
L
L
DeTeresa
R
R
Terry
R D
RD
Saitoh
T
T
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000595:Amino Acid Sequence; D000906:Antibodies; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology; D010455:Peptides / Q000138:chemical synthesis; D011493:Protein Kinase C / Q000032:analysis* / Q000276:immunology; D012016:Reference Values
D000906:Antibodies; D007527:Isoenzymes; D010455:Peptides; D011493:Protein Kinase C