Twenty Alzheimer's disease (AD) patients with defined apolipoprotein E (APOE), alpha1-antichymotrypsin (ACT) and presenilin-1 (PS-1) intronic genotypes were examined to quantify the regional cerebral metabolic rate of glucose (rCMRglc) using positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). The frontal rCMRglc was significantly increased in patients with the APOE epsilon4 allele in a dose-dependent fashion. In contrast, the temporo-parietal rCMRglc was significantly reduced in ACT type A allele (ACT*A) carriers compared with those in non-ACT*A carriers. The PS-1 type 1 intronic allele had no significant effects on rCMRglc in any cerebral region. These results suggest that both the APOE and ACT genes may play a distinct role in the progression of AD as monitored by imaging studies of cerebral glucose utilization.