Cyclooxygenase-1 in human Alzheimer and control brain: Quantitative analysis of expression by microglia and CA3 hippocampal neurons

Epidemiological and clinical studies suggest that nonsteroidal anti-inflamm atory drugs (NSAIDs) that inhibit cyclooxygenase (COX) slow the progression and delay the onset of Alzheimer disease (AD). Two isoforms of cyclooxygen ase have been identified. Although much effort has recently been focused on the inducible COX-2 isoform, little is known about COX-1 expression in hum an brain. We report that COX-1 message and immunoreactivity are localized t o human hippocampal CA3 and CA4 neurons, granular neurons in neocortical la yer IV, and occasional cortical pyramidal neurons. Quantitative in situ hyb ridization showed no differences between COX-1 mRNA levels in control and A D CA3 hippocampal neurons. COX-1 immunoreactivity was also present in micro glial cells in gray and white matter in all brain regions examined. COX-1 a ppeared to be expressed in microglial cells regardless of their activation state as determined by HLA-DR immunostaining. However, COX-1 immunopositive microglia were found in association with A beta plaques, and the density o f COX-1 immunopositive microglia in AD fusiform cortex was increased. This pattern suggests an overall increase of COX-1 expression in AD. Currently u sed NSAIDs inhibit both isoforms of cyclooxygenase. The present study shows that COX-1 is widely expressed in human brain, and raises the possibility that COX-1 may contribute to CNS pathology.