Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology |
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Authors: | Xiang Zhongmin Ho Lap Yemul Shrishailam Zhao Zhong Qing Wein Pompl Patrick Kelley Kevin Dang Anju Qing Weiping Teplow David Pasinetti Giulio Maria |
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Institution: | Neuroinflammation Research Laboratories, Department of Psychiatry, and Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. |
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Abstract: | Several epidemiologic studies have reported that cyclooxygenase (COX) inhibitors prevent/delay the onset of Alzheimer's disease (AD). Recent experimental studies suggest that these compounds can also diminish amyloid-beta (Abeta) neuropathology in rodent models of AD. To explore the relationship of COX expression to Abeta neuropathology, we crossed mice expressing both mutant amyloid precursor protein K670N/M671L (APP(swe)] and mutant PS1 (A246E) with mice expressing human COX-2 selectively in neurons. We show here that human COX-2 expression in APP(swe)/PS1/COX-2 mice induces potentiation of brain parenchymal amyloid plaque formation and a greater than twofold increase in prostaglandin E2 production, at 24 months of age. This increased amyloid plaque formation coincided with a preferential elevation of Abeta1-40 and Abeta1-42 with no change in total amyloid precursor protein (APP) expression/content in the brain. Collectively these data suggest that COX-2 influences APP processing and promotes amyloidosis in the brain. |
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