Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease.
Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to delay the onset of Alzheimer's disease (AD). NSAIDs inhibit cyclooxygenase (COX), of which two isoforms exist. We report decreased neuronal COX-2 expression in AD subjects relative to nondemented controls using qualitative analysis of COX-2 immunoreactivity and quantification of COX-2 positive neurons in different hippocampal subfields. These changes also occurred in subjects with other dementia and thus may not be disease specific. The proportion of COX-2 positive neurons decreased in subjects with clinical dementia rating (CDR) 5 but not CDR 4, suggesting that this was a late event in the course of the disease. Furthermore, COX-2 was not preferentially associated with paired helical filament immunoreactivity, a marker of neuronal pathology. COX-2 immunoreactivity was also observed in astrocytes and cerebrovasculature. Indeed, the density of COX-2 immunopositive astrocytes was increased in AD temporal cortex. Based on our findings, it is unlikely that neuronal COX-2 contributes to pathology in end stage AD; however, COX-2 in other cell types may participate in the inflammation-related response associated with the disease.
Yermakova
A V
AV
Departments of Neurobiology & Anatomy and Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
O'Banion
M K
MK
D000368:Aged; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000918:Antibody Specificity; D001253:Astrocytes / Q000473:pathology; D001344:Autopsy; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2; D015536:Down-Regulation / Q000235:genetics*; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D011180:Postmortem Changes; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics; D016875:tau Proteins / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D016875:tau Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases