Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer's disease

Lap Ho, Cristiana Pieroni, David Winger, Dushyant P. Purohit, Paul S. Aisen, Giulio Maria Pasinetti

Research output: Contribution to journalShort surveypeer-review

234 Scopus citations

Abstract

Cyclooxygenase-2 (COX-2), a key enzyme in prostanoid biosynthesis, may represent an important therapeutic target in Alzheimer's disease (AD). In the present study, we explored the regulation of COX-2 in the hippocampal formation in sporadic AD. Using semiquantitative immunocytochemical techniques, we found that in AD cases (vs. age-matched controls) neurons of the CA1-CA4 subdivisions of the hippocampal pyramidal layer showed elevation of COX-2 signal; COX-2 levels correlated with amyloid plaque density. In contrast, the level of COX-2 immunostaining in the dentate gyrus granule neurons was not elevated in AD. No expression of COX-2 in cells with glial morphology was found in any case examined. In parallel, in vitro studies found that neurons derived from transgenic mice with neuronal overexpression of COX-2 are more susceptible to β-amyloid (Aβ) toxicity, with potentiation of redox impairment. The results indicate elevated expression of neuronal COX-2 in subregions of the hippocampal formation in AD and that such elevation may potentiate Aβ-mediated oxidative stress.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalJournal of Neuroscience Research
Volume57
Issue number3
DOIs
StatePublished - 1 Aug 1999

Keywords

  • Alzheimer's disease
  • Cyclooxygenase inflammation
  • NSAIDs
  • Oxidative stress

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