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 activat ion of cylooxygenase (COX). In the present study the expression of COX-1 an d COX-2 in AD and non-demented control temporal and frontal cortex was inve stigated using immunohistochemistry. COX-1 expression was detected in micro glial cells, while COX-2 expression was found in neuronal cells. In AD brai ns, COX-1-positive microglial cells were primarily associated with amyloid beta plaques, while the number of COX-2-positive neurons was increased comp ared to that in control brains. No COX expression was detected in astrocyte s. In vitro, primary human microglial and astrocyte cultures, and human neu roblastoma cells (SK-N-SH) were found to secrete prostaglandin E-2 (PGE(2)) , especially when stimulated. PGE(2) synthesis by astrocytes and SK-N-SH ce lls was stimulated by interleukin-1 beta. Microglial cell PGE(2) 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 indicat ions that these cells express COX-1 or COX-2 in vivo. The different distrib ution 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.