Objective Alzheimers disease (AD) is one of the most common age-related neurodegenerative diseases.The brain of AD patients show a chronic inflammatory response characterized by activated glial cells and increased expression of cytokines, chemotactic factors and complement factors.However, whether the inflammatory response in AD pathologic process is a powerful pathogenetic force or a concomitant symptom remains unclear.Epidemiological studies have demonstrated that there is a reduced risk for AD patients using nonsteroidal anti-infiammatory drugs (NSAIDs).This present study is using ibuprofen, which is one of the most commonly used NSAIDs, to evaluate whether it could affect AD-like pathology in 3-month-old (mild inflammatory response and memory impairment) and 6-month-old (intensive inflammatory response and memory impairment) presenilin 1 and 2 conditional double knockout (cDKO) mice.Methods Conditional DKO mice were obtained by crossing the forebrain specific PS 1 heterozygous knockout mice with conventional PS2 heterozygous knockout mice on B6/CBAF 1 genetic background.Mice with the Cre transgene, fPS1/fPS1, and PS2-/-served as cDKO, their litterrnates (no Cre, fPS1/+ and PS2+/+ or fPS1/+ and PS2+/-) served as controls.Mice were housed under 20-26 ℃ temperature and 40%-70% humidity with 12 hrs light/dark cycles, and all the experiments were approved by the Animal Ethics Committee in ECNU, China.cDKO mice were employed a dose of dietary ibuprofen (375 ppm) at the early stage (3-month-old) and the middle stage (6-month-old), respectively, continuously treated for 6 months, while for the control group, the littermate cDKO mice received standard diet.Then a series of behavioral tests were performed to assay the ibuprofen effects on cognitive impairment in cDKO mice.Results (1) The 3-month-old cDKO mice showed improved recognition memory in 1-hour novel object recognition after the ibuprofen treatment.(2) The 6-month-old cDKO mice show improved memory in 1-hour novel object recognition, enhanced contextual fear memory and cued fear memory after the ibuprofen treatment.Conclusion Ibuprofen, as one of the most commonly used NSAIDs, could rescue cognitive impairment to a certain degree.More effects of ibuprofen on other pathologic process in cDKO mice need to be confirmed.