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

Neuroscience. 1998 Nov;87(2):319-24. doi: 10.1016/s0306-4522(98)00218-8.


Many epidemiological studies suggest that use of nonsteroidal anti-inflammatory drugs delays or slows the clinical expression of Alzheimer's disease, but the mechanism by which these drugs might affect pathophysiological processes relevant to Alzheimer's disease has been unclear. 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. Cyclooxygenase-2 has been identified in rodent brain. Excitotoxic lesions cause up-regulation of cyclooxygenase-2 expression coincident with the onset of expression of markers of apoptosis; 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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / enzymology*
  • Blotting, Northern
  • Blotting, Western
  • Cyclooxygenase 2
  • Humans
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Membrane Proteins
  • Neurons / enzymology
  • Prefrontal Cortex / enzymology*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • RNA, Messenger / biosynthesis


  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases