Racial and Ethnic Disparities in Alzheimer's Disease: A Literature Review. Genetics

02/01/2014

APOE is a gene that comes in a normal or neutral form (allele), known as E3, and two variants, E2 and E4, which have been implicated in vascular and Alzheimer's diseases. The E4 variant is the most important known genetic risk factor for Alzheimer's disease.

In a recent review and meta-analysis, E4 has been shown to be associated with about 65%-75% of cases of sporadic (not genetically inherited) Alzheimer's disease and up to 20% of all dementias (Crean et al., 2011). The meta-analysis found that 39% of Alzheimer's disease patients from Asian countries carried the E4 allele; 43% of patients from Southern Europe and the Mediterranean; 54% from Central Europe; 59% from North America; and 64% from Northern Europe.

Having one or two alleles, or forms, of the APOE gene is a major predictor of Alzheimer's disease in Whites but a weak or inconsistent predictor in African Americans and Hispanics (Crean et al., 2011). In an earlier meta-analysis, the prevalence of E4 among those with Alzheimer's disease was highest in Whites (37%), followed by African Americans (32%), Japanese (28%), and Hispanics (19%) (Farrer et al., 1997). Two genetic studies have found that the E4/E4 genotype is more likely to be associated with dementia in African Americans than in Whites (Green et al., 2002; Maestre et al., 1995), but a third found that one or more E4 alleles was not associated with increased risk in African Americans or Hispanics, but was in Whites (Maestre et al., 1995). The E2/E4 and E3/E4 genotypes have been shown to be associated with an increased risk of Alzheimer's in Whites, but not African Americans, in one study (Green et al., 2002). However, an earlier study found an increased risk associated with the E2/E3 genotype among African Americans, but not Whites (Maestre et al., 1995).

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