Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and α₁-antichymotrypsin type A allele in Alzheimer's disease

Twenty patients with Alzheimer's disease (AD) with defined apolipoprotein E (APOE), α₁-antichymotrypsin (ACT) and presenilin-1 (PS-1) intronic genotypes were examined to quantify the regional cerebral metabolic rate of glucose (rCMRglc) by 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 ε4 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 did not have any 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.