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

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. J. Neurosci. Res. 57:295–303, 1999. © 1999 Wiley-Liss, Inc.