The learning and memory impairment of presenifin 2 transgenic mice was mentioned previously. In this study, exposing the presenifin 2 transfected PC12 cells to the 50 mu M A beta(25-35), 30 mM L-glutamate and 50 mu M H2O2 resulted in significant increase 8-oxodG and p53 levels of the cells expressing the mutant gene. The increase was also found in the mutant presenilin 2 transgenic mice brains age-dependently in comparison to that in the wild-type presenilin 2-transgenic mice and non-transgenic ones. These findings indicated that mutant presenilin 2 clearly increases oxidative stress and p53 expression, which could be implicated in promoting mutant presenilin 2-induced neurodegeneration in Alzheimer's disease, and the influence of mutant presenilin 2 in Alzheimer's disease may be brain regional and age related effects. (c) 2007 Elsevier Inc. All rights reserved.