COX-2 elevation is critical for elevating the production of PGE2 and 15d-PGJ2 as well as for the deposition of Aβ, which accelerates the cognitive decline of APP/PS1 mice. COX-2 mice were bred with APP/PS1 mice to obtain the COX-2/APP/PS1 mice, and genotyping was performed at the age of 1 month. Performance on the (A) Morris water maze test and (B) nest construction was analyzed. (C, D) Escape latency and path length were determined in the first 6 days of hidden platform tests. (E) The probe trials were conducted on day 7. (F) Nest construction was quantified in WT, APP/PS1, and COX-2/APP/PS1 mice. The nesting scores were analyzed by the methods described in the “Experimental Procedures.” (G, H) The right halves of brains were stained with an Aβ antibody before analysis by microscopy. (I, J) The production of PGE2 and 15d-PGJ2 in the CSF of APP/PS1 and COX-2/APP/PS1 mice was determined by PGE2 and 15d-PGJ2 ELISA kits. *p < 0.05; **p < 0.01; ***p < 0.001 compared with the WT group. #p < 0.05; ##p < 0.01; ###p < 0.001 compared with APP/PS1 mice (n = 6)