Elsevier

Neuroscience

Volume 87, Issue 2, 20 July 1998, Pages 319-324
Neuroscience

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

https://doi.org/10.1016/S0306-4522(98)00218-8Get rights and content

Abstract

Many epidemiological studies suggest that use of non-steroidal 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, 15Cyclooxygenase-2 has been identified in rodent brain.1, 8, 21, 22Excitotoxic 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-2 expression in Alzheimer's disease frontal cortex. Further, we found that synthetic β-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.

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Acknowledgements

This work was supported by AG13799, AG14239 to GMP, by AG05138 (ADRC of Mount Sinai) to K. L. Davis and by AG02219 (program project) to R. Mohs. The authors thank Drs K. L. Davis, H. Haroutunian, D. Perl and D. P. Purohit (Mount Sinai ADRC) for human brain autopsy material. The authors also thank Dr Jose Freire-Moar for superb technical assistance.

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