Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi-ethnic sample

Objective: This study examined the association between the Apolipoprotein-E ε4 allele (APOE ε4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients. Design: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. Subjects: A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n=359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. Measures: Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member. Results: A significant relationship was discovered between APOE ε4 and age of onset for WNH, with lower ages of onset among patients carrying the ε4/ε4 and ε3˜/ε4 genotypes in relation to patients with the ε3/ε3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among ε4 positive patients (ε2/ε4, ε3/ε4 and ε4/ε4 genotypes) in comparison to ε4 negative patients (ε2/ε2, ε2/ε3 and ε3/ε3 genotypes). Conclusion: The association between the ε4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S.