The effect of APOE ε4 allele on cerebral glucose metabolism in AD is a function of age at onset

Background: Although the APOE ε4 allele is a well-known risk factor for developing AD, the impact of the E4 allele on clinical manifestations in patients with AD is still controversial. One possible reason for this controversy is that previous studies did not consider the effect of patient age at symptom onset. Objective: To investigate the possible impact of patient age at onset of AD on the effect of APOE genotype on regional cerebral glucose metabolism (rCMRglc). Methods: The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE ε4/4 and APOE ε3/3 alleles in early-onset (≤65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE ε4/4 and APOE ε3/3 alleles were comparable for age at onset, age at examination, sex, disease duration, education level, and severity of dementia. Results: In the early-onset group, the patients with the APOE ε4/4 genotype showed a significant decrease of rCMRglc in the medial temporal lobe and a significant increase of rCMRglc in the inferior parietal and posterior temporal cortices as compared with those patients with the APOE ε3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE ε4/4 and APOE ε3/3 alleles. Conclusions: The current findings indicate that the impact of the APOE ε4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.