Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain

Many epidemiological studies suggest that use of nonsteroidal anti-inflammatory drugs delays or slows the clinical expression of Alzheimer's disease,(13) but the mechanism by which these drugs might affect pathophysiological processes relevant to Alzheimer's disease has been unclear.(2) Non-steroidal anti-inflammatory drugs are presumed to act by inhibiting cyclooxygenase, a key enzyme in the metabolism of membrane-derived arachidonic acid into prostaglandins, In recent years, two distinct isoforms of cyclooxygenase have been characterized, a constitutive form, cyclooxygenase-1, and a mitogen-inducible form, cyclooxygenase-2.(4,10,15) Cyclooxygenase-2 has been identified in rodent brain.(1,8,21,22) Excitotoxic lesions cause up-regulation of cyclooxygenase-2 expression coincident with the onset of expression of markers of apoptosis;(21) cyclooxygenase-2 thus represents a possible target of non-steroidal anti-inflammatory drug action in neurodegenerative mechanisms. In the present study, we examined cyclooxygenase-2 gene expression in Alzheimer's disease and control cases, We found up-regulation of cyclooxygenase-a expression in Alzheimer's disease frontal cortex. Further, we found that synthetic beta-amyloid peptides induced cyclooxygenase-2 expression in SH-SY5Y neuroblastoma cells in vitro, suggesting a mechanism for cyclooxygenase-2 up-regulation in Alzheimer's disease, These findings support the investigation of selective cyclooxygenase-2 inhibitors for the treatment of Alzheimer's disease. (C) 1998 IBRO. Published by Elsevier Science Ltd.