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The apolipoprotein E ε4 allele was associated with Alzheimer's disease in white but not in African-American or Hispanic people
  1. Robert Clarke, MD
  1. University of Oxford Oxford, UK

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 Question Is the risk of Alzheimer's disease associated with the apolipoprotein E ε4 (APOE ε4) allele lower for African-American and Hispanic people than for white people?

    Design

    5 year population based cohort study.

    Setting

    New York City, USA.

    Participants

    2128 of 4865 eligible, healthy participants ≥65 years of age who had no dementia, lived in areas of a community that corresponded to 3 neighbouring US zip codes, and received Medicare had an initial interview. 1079 participants (mean age 75 y; 68% women; 17% African-American, 61% Hispanic, 22% white) completed follow up.

    Assessment of risk factors

    Interviews and standardised clinical assessments were used to assess general health and function. Ethnic group, family history, and the presence of APOE ε4 alleles were also assessed.

    Main outcome measure

    Relative risk for Alzheimer's disease. Diagnosis of Alzheimer's disease was obtained by a consensus of physicians and neuropsychologists who were blind to APOE genotypes and used preset criteria.

    Main results

    Probable or possible Alzheimer's disease developed in 21% of participants and occurred more frequently among African-American and Hispanic participants than among white participants (10.5% and 7.6% v 3.4% for probable Alzheimer's disease and 18.8% and 14.4% v 6.3% for possible Alzheimer's disease, p=0.001 for both comparisons). When participants with ≥1 APOE ε4 alleles were compared with those with APOE ε3/ε3 genotypes, the relative risk of Alzheimer's disease to age 90 years was increased for white but not for African-American or Hispanic participants (table). Among participants with ≥1 APOE ε4 alleles, the relative risk of Alzheimer's disease to age 90 years did not differ for African-American or Hispanic participants compared with white participants (table) and remained after the results were adjusted for sex and education. Among participants without an APOE ε4 allele, the relative risk of Alzheimer's disease to age 90 years, adjusted for age and sex, was increased fourfold for African-American and twofold for Hispanic participants compared with white participants (table). Multivariate analyses showed that family history of illnesses like Alzheimer's disease, history of myocardial infarction and head injury, and smoking history did not influence the risk of developing Alzheimer's disease.

    Relative risk of Alzheimer's disease across ethnic groups

    Conclusions

    Apolipoprotein E ε4 allele was associated with the development of Alzheimer's disease in white people but not in African-American or Hispanic people. African-American and Hispanic people had an increased risk of developing Alzheimer's disease compared with white people.

    Commentary

    Identifying genetic factors associated with Alzheimer's disease may yield clues to the underlying cause and open the way to possible therapeutic targets that might alter the clinical course of the disease or prevent it from occurring. The APOE ε4 allele is widely viewed as 1 of the most important risk factors of Alzheimer's disease in both sexes and in all ethnic groups. A recent meta-analysis which reviewed individual participant data from 40 research teams who contributed data on the APOE genotype in 6000 people with Alzheimer's disease and 8600 controls showed a substantial association of this genotype in all ethnic groups.1 The meta-analysis which included data on 235 African-American and 261 Hispanic cases with Alzheimer's disease did, however, suggest that the association of APOE with Alzheimer's disease in these populations was somewhat attenuated compared with white cases.

    The report by Tang et al which studied these associations in 106 African-American and 290 Hispanic cases with Alzheimer's disease argued against any such association and suggested that other genes or risk factors may contribute to this disease in these populations. It is unclear the extent to which the discrepant results of individual studies may be explained by chance, selection bias, or differential survival. Nevertheless, it is likely that Alzheimer's disease has a multifactorial aetiology and that some environmental, nutritional, or lifestyle factors may interact with genetic factors in susceptible people to trigger the onset of this disease.2 Vascular risk factors may be particularly relevant in the search for possible therapeutic targets of Alzheimer's disease.

    References

    View Abstract

    Footnotes

    • Sources of funding: National Institutes of Health; Charles S Robertson Memorial Gift for Alzheimer's Disease Research from the Banbury Fund; Blanchette Hooker Rockefeller Fund.

    • For correspondence: Dr R Mayeux, Gertrude H Sergievsky Center, 630 West 168th Street, Columbia University, New York, NY 10032, USA. Fax +1 212 305 2518.

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