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

L Ho, C Pieroni, D Winger, DP Purohit… - Journal of …, 1999 - Wiley Online Library
L Ho, C Pieroni, D Winger, DP Purohit, PS Aisen, GM Pasinetti
Journal of neuroscience research, 1999Wiley Online Library
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 …
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.
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