Elevated protein levels of protein phosphatases PP-2A and PP-2B in astrocytes of Alzheimer's disease temporal cortex.
Previous studies have shown that activities of the protein phosphatases PP-2A and PP-2B towards the microtubule associated protein tau are reduced in Alzheimer's disease (AD) frontal cortex (Gong et al., 1993, 1995), suggesting that PP-2A and PP-2B are involved in the hyperphosphorylation of tau in AD. Most recently, we found that protein levels of PP-2A and PP-2B are elevated in postsynaptic supernatant (S2) fractions 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 numbers 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 controls. 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 from the same brains. These results suggest that astrogliosis probably accounts for the increased levels of PP-2A and PP-2B in the S2 fraction in AD brain and that the levels of these enzymes per neuron are likely to be decreased.
Pei
J J
JJ
Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Novum, KFC, Huddinge, Sweden.
Grundke-Iqbal
I
I
Iqbal
K
K
Bogdanovic
N
N
Winblad
B
B
Cowburn
R F
RF
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001253:Astrocytes / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013702:Temporal Lobe / Q000201:enzymology* / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D010749:Phosphoprotein Phosphatases