Exploratory Study of Apolipoprotein E ε4 Genotype and Risk of Alzheimer's Disease in Mexican Hispanics

Abstract

To the Editor: Hispanics are 1.5 times more likely to develop Alzheimer's disease (AD) than White non-Hispanics1. A community-based study reported that the prevalence of AD is higher in Hispanics than in White non-Hispanics2. Interestingly, a recent study found that the average proportion of Amerindian genetic ancestry in AD cases was a third of that observed in the cognitively intact controls3. These findings suggest that Amerindian ancestry confers a protective effect against disease onset. Hispanics are a mixture of European, African, and Amerindian genomes, with percentages depending on the country of origin4. Individuals of Mexican origin generally are of Amerindian ancestry, while those of Caribbean origin, for example, have more African ancestry5,6. Therefore, the question arises as to whether Mexican Hispanics differ in their susceptibility to AD. The Apolipoprotein E (APOE) gene, with its three common alleles (e2, e3, e4), is involved in cholesterol transport and other biologic pathways potentially relevant to AD7 and has been consistently associated with an increased risk of AD8. Studies indicate that the APOE genetic risk variants may not carry the same risk for Hispanics as for White non-Hispanics. A meta-analysis found an association between the APOE-e4 allele and AD, although the risk conveyed by the APOE-e4 allele frequency was found to be lower in Hispanics, predominately Caribbean origin, than in White non-Hispanics9. Another study of Hispanic Americans of predominantly Caribbean origin showed a smaller relative risk of AD conveyed by the APOE-e4 allele in Hispanics than in White non-Hispanics10. To our knowledge, Mexican Hispanics have not been studied as a single group to determine the associated risk between the APOE-e4 allele and AD onset.