Early regional cerebral glucose hypometabolism in transgenic mice overexpressing the V717F beta-amyloid precursor protein

In the present study, we examined whether the relative levels of regional b rain [C-14]2-deoxyglucose (2-DG) uptake are altered in a transgenic mouse m odel 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, d entate gyrus and parietal cortex of 3-month-old transgenic mice as compared with wild-type littermates. In 10-month-old transgenic mice, these alterat ions also extend to the CA3 hippocampal region, the cingulate, retrosplenia l, occipital and temporal cortices, suggesting an age-dependent decrease in the regional 2-DG uptake. These results suggest that expression of a mutat ed APP gene induces an early regional cerebral hypometabolism independently of amyloid deposition per se. (C) 1999 Elsevier Science Ireland Ltd. All r ights reserved.