Effects of chronic lithium treatment on platelet PKC isozymes in Alzheimer's and elderly control subjects.

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.003). After 3 weeks of lithium treatment, AD patients had significantly less membrane-associated PKC alpha (P < 0.002), epsilon (P < 0.003), and zeta (P < 0.001) than normals. This is the first report of a difference in PKC in blood cells between AD and control subjects. These findings appear to indicate that some PKC isozymes may be differentially regulated in AD versus elderly controls, at least as evidenced in this peripheral cellular system.