Dietary influences on Alzheimer disease (AD) are gaining recognition. Because many aging processes are attenuated in laboratory mammals by caloric restriction (CR), we examined the effects of short-term CR in two AD-transgenic mice, APP swe/ind (J20) and APP swe +PS1 M146L (APP+PS1). CR substantially decreased the accumulation of Aβ-plaques in both lines: by 40% in APP swe/ind (CR, 6 weeks), and by 55% in APP+PS1 (CR, 14 weeks). CR also decreased astrocytic activation (GFAP immunoreactivity). These influences of CR on AD-transgenic mice are consistent with epidemiological reports that show that high caloric diets associate with the risk of AD, and suggest that dietary interventions in adult life might slow disease progression.