This has been shown in cognitively normal humans,4,7,10,11 MCI patients,8,12 APOE ε4 carriers11 and familial AD mutation carriers,6 as well as mouse models of AD,5,19 and may be driven by a reactivity-induced increase in glial metabolism4,5 or network disinhibition.13 These hypermetabolic regions also appear to be susceptible to accelerated pathology at later stages in longitudinal imaging.33 Our data provide convincing evidence to support this hypermetabolic phase in early AD and are the first to do so in a rat model. This evidence concerns the gene APOE and Alzheimer disease.