Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer's disease.
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 beta-amyloid (Abeta) 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 Abeta-mediated oxidative stress.
Ho
L
L
Neuroinflammation Research Laboratories of the Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York 10029, USA. gp2@doc.mssm.edu
Pieroni
C
C
Winger
D
D
Purohit
D P
DP
Aisen
P S
PS
Pasinetti
G M
GM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001284:Atrophy / Q000201:enzymology; D016022:Case-Control Studies; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*; D009498:Neurotoxins / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D008565:Membrane Proteins; D009498:Neurotoxins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases