Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals.
Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain of patients with Alzheimer disease (AD). Previous studies have shown (i) that in vitro tau can be phosphorylated to an Alzheimer abnormally phosphorylated state-like protein by proline-directed protein kinases MAP kinase and p34cdc2, and (ii) that the AD abnormally phosphorylated tau can be in vitro dephosphorylated by protein phosphatases PP-2B, PP-2A and PP-1 and not by PP-2C. However, to have a direct effect on the regulation of phosphorylation of tau, these enzymes should be present in the affected neurons. In the present study immunocytochemical localization of protein phosphatases PP-1, PP-2A, PP-2B and PTP, and protein kinases MAP kinase and p34cdc2 were studied in the hippocampal formation of AD and as a control in non-demented elderly patients. All the protein phosphatases and protein kinases studied were localized to both granular and pyramidal neurons. In the pyramidal neurons, the enzymes staining was observed in neuronal soma and neurites. PTP-1B, PP-1 and PP-2A were also highly expressed in microglia. The topographical distributions of all the enzymes studied were similar, i.e. the intensity of immunostaining in hippocampus in end-plate (CA3 and CA4) > prosubiculum, subiculum > entorhinal cortex > dentate gyrus > CA2 > CA1. Furthermore, the expression of all the enzymes was also observed in the tangle-bearing neurons. The PP-2B staining of the tangle-bearing neurons was weaker than the unaffected neurons in the same tissue section field in AD cases.
Pei
J J
JJ
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Sersen
E
E
Iqbal
K
K
Grundke-Iqbal
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000201:enzymology / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D011494:Protein Kinases / Q000096:biosynthesis*; D017966:Pyramidal Cells / Q000201:enzymology; D016875:tau Proteins / Q000378:metabolism
D016875:tau Proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases