Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-β1-42

Epidemiological studies have shown that the risk of developing Alzheimer's disease is reduced by the chronic use of classical non-steroidal anti-inflammatory drugs (NSAIDs), drugs that inhibit the cyclo-oxygenase (COX) enzymes that convert arachidonic acid to prostaglandins. In the present study, human SH-SY5Y neuroblastoma cells or murine primary cortical neurones treated with NSAIDs were protected against the otherwise toxic effects of amyloid-beta(1-42). COX-1 selective inhibitors provided greater protection than did COX-2 selective inhibitors or lipoxygenase inhibitors, suggesting that activation of COX-1 is required for amyloid-beta(1-42)-induced neurotoxicity. Although the production of neuronal prostaglandin E-2 in response to amyloid-beta(1-42) was reduced by the presence of COX-1 inhibitors, no neurotoxic effects of prostaglandin E-2, or any other prostaglandin, were observed.