ELEVATED PROTEIN-LEVELS OF PROTEIN PHOSPHATASES PP-2A AND PP-2B IN ASTROCYTES OF ALZHEIMERS-DISEASE TEMPORAL CORTEX

Previous studies have shown that activities of the protein phosphatase s PP-2A and PP-2B towards the microtubule associated protein tau are r educed in Alzheimer's disease (AD) frontal cortex (Gong et al., 1993, 1995), suggesting that PP-2A and PP-2B are involved in the hyperphosph orylation of tau in AD. Most recently, we found that protein levels of PP-2A and PP-2B are elevated in postsynaptic supernatant (S2) fractio ns prepared from AD temporal cortex, and that the activities of these enzymes were not significantly different between AD and control cases (Pei et al., in press). In the present study, we found that astroglia positive for PP-2A and PP-2B immunoreactivities were greater in number s in AD medial temporal cortex, compared to controls. GFAP levels, as determined by indirect ELISA, were approximately 1.5 times greater in the P1 (500 x g) fraction from AD temporal cortex, compared to control s. GFAP levels in the P1 fraction showed significant correlations with PP-2A and PP-2B levels in the postsynaptic S2 (20,000 x g) fraction f rom the same brains. These results suggest that astrogliosis probably accounts for the increased levels of PP-2A and PP-2B in the S2 fractio n in AD brain and that the levels of these enzymes per neuron are like ly to be decreased.