The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease (AD) in the Volga German families. We have generated transgenic mouse lines overexpressing human wild‐type or mutant PS2 under transcriptional control of the chicken β‐actin promoter. In the brains of transgenic mice, the levels of human PS2 mRNA were found to be five‐ to 15‐fold higher than that of endogenous mouse PS2 mRNA. The amyloid β‐protein (Aβ) 42 levels in the brains of mutant PS2 transgenic mice were higher than those in wild‐type PS2 transgenic mice at the age of 2, 5, or 8 months. In addition, the Aβ42 levels appeared to increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild‐type transgenic mice between the ages of 5 and 8 months. There was no definite difference in the levels of N‐terminal and C‐terminal fragments between wild‐type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months. These data show a definite effect of the PS2 mutation on an age‐dependent increase of Aβ42 content in the brain.