To test the effects of APOE4 on brain metabolism in the absence of AD pathology, we studied young (mean age = 8 months; 6 APOE3, and 8 APOE4 males) and old (mean age = 20 months; 7 APOE3, and 8 APOE4 males) APOE-targeted replacement mice, which express the human APOE gene in place of the endogenous mouse Apoe gene37, 38. This evidence concerns the gene APOE and Alzheimer disease.