Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to delay the onset of Alzheimer's disease (AD). NSAIDs inhibit cyclooxygenase (COX), of which two isoforms exist. We report decreased neuronal COX-2 expression in AD subjects relative to nondemented controls using qualitative analysis of COX-2 immunoreactivity and quantification of COX-2 positive neurons in different hippocampal subfields. These changes also occurred in subjects with other dementia and thus may not be disease specific. The proportion of COX-2 positive neurons decreased in subjects with clinical dementia rating (CDR) 5 but not CDR 4, suggesting that this was a late event in the course of the disease. Furthermore, COX-2 was not preferentially associated with paired helical filament immunoreactivity, a marker of neuronal pathology. COX-2 immunoreactivity was also observed in astrocytes and cerebrovasculature. Indeed, the density of COX-2 immunopositive astrocytes was increased in AD temporal cortex. Based on our findings, it is unlikely that neuronal COX-2 contributes to pathology in end stage AD; however, COX-2 in other cell types may participate in the inflammation-related response associated with the disease.