title: Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.
abstract: Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Our studies showed that loss of either COX-1 or COX-2 gene did not alter amyloid burden in brains of the APP transgenic mice. However, one marker of microglial activation (CD45) was decreased in brains of COX-1 deficient/APP animals and showed a strong trend in reduction in COX-2 deficient/APP animals. These results suggest that COX activity and amyloid deposition in brain are likely independent processes. Further, if NSAIDs do causally reduce the risks of AD, then our findings indicate that the mechanisms are likely not due primarily to their inhibition on COX or γ-secretase modulation activity, the latter reported recently after acute dosing of ibuprofen in humans and nonhuman primates.
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA; Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 14584, Republic of Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Park
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA; Université de Montpellier, Montepellier, F-34095, France; Inserm, U 1198, Montepellier, F-34095, France; EPHE, Paris, F-75014, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chevallier
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA.
authors.forename: Karishma
authors.initials: K
authors.lastname: Tejwani
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Hung
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Neuroscience, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Golde
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92037, USA; Departments of Medicine and Physiology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, 117597, Singapore. Electronic address: edkoo@ucsd.edu.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Koo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse
keywords: Alzheimer's disease; Amyloid β protein; Cyclooxygenase; Microglia; Transgenic mice