Cyclooxygenase expression in microglia and neurons in Alzheimer's disease and control brain.
Epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) lower the risk of developing Alzheimer's disease (AD). Most NSAIDs act upon local inflammatory events by inhibiting the expression or activation of cylooxygenase (COX). In the present study the expression of COX-1 and COX-2 in AD and non-demented control temporal and frontal cortex was investigated using immunohistochemistry. COX-1 expression was detected in microglial cells, while COX-2 expression was found in neuronal cells. In AD brains, COX-1-positive microglial cells were primarily associated with amyloid beta plaques, while the number of COX-2-positive neurons was increased compared to that in control brains. No COX expression was detected in astrocytes. In vitro, primary human microglial and astrocyte cultures, and human neuroblastoma cells (SK-N-SH) were found to secrete prostaglandin E2 (PGE2), especially when stimulated. PGE2 synthesis by astrocytes and SK-N-SH cells was stimulated by interleukin-1beta. Microglial cell PGE2 synthesis was stimulated by lipopolysaccharide only. Although astrocytes are used in studies in vitro to investigate the role of COX in AD, there are no indications that these cells express COX-1 or COX-2 in vivo. The different distribution patterns of COX-1 and COX-2 in AD could implicate that these enzymes are involved in different cellular processes in the pathogenesis of AD.
Hoozemans
J J
JJ
Department of Pathology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands. jjm.hoozemans@azvu.nl
Rozemuller
A J
AJ
Janssen
I
I
De Groot
C J
CJ
Veerhuis
R
R
Eikelenboom
P
P
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases