Journal of Neuroscience, Vol 10, 2113-2124, Copyright © 1990 by Society for Neuroscience
Differential involvement of protein kinase C isozymes in Alzheimer's disease
E Masliah, G Cole, S Shimohama, L Hansen, R DeTeresa, RD Terry and T Saitoh
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093.
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.
Previous Article | Next Article
