In the present study, we examined whether the relative levels of regional brain [14C]2-deoxyglucose (2-DG) uptake are altered in a transgenic mouse model of Alzheimer's disease which overexpresses a mutated form of the human beta-amyloid precursor protein (mutation V717F). We show that the relative levels of 2-DG uptake are significantly reduced in the septum, thalamus, dentate gyrus and parietal cortex of 3-month-old transgenic mice as compared with wild-type littermates. In 10-month-old transgenic mice, these alterations also extend to the CA3 hippocampal region, the cingulate, retrosplenial, occipital and temporal cortices, suggesting an age-dependent decrease in the regional 2-DG uptake. These results suggest that expression of a mutated APP gene induces an early regional cerebral hypometabolism independently of amyloid deposition per se.