Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology.
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.
Xiang
Zhongmin
Z
Neuroinflammation Research Laboratories, Department of Psychiatry, and Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Ho
Lap
L
Yemul
Shrishailam
S
Zhao
Zhong
Z
Qing
Wein
W
Pompl
Patrick
P
Kelley
Kevin
K
Dang
Anju
A
Qing
Weiping
W
Teplow
David
D
Pasinetti
Giulio Maria
GM
D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000682:Amyloid; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone