African-Americans with APOE gene variant also at risk for Alzheimer's

Friday, June 21, 2002

JACKSONVILLE, Fla., June 21, 2002 — Researchers at Mayo Clinic in Jacksonville have concluded that a variant of the gene known to be the leading genetic risk factor in developing Alzheimer's disease (AD) among Caucasians is also an important risk factor among African-Americans.

The Mayo researchers, in collaboration with colleagues at five other academic medical centers, studied the distribution of the e4 variation of the apolipoprotein E (APOE) gene in three groups of African-Americans: 338 with AD; 301 cognitively healthy, unrelated individuals; and 108 siblings of 88 of the people with AD.

The researchers concluded that the presence of one or two copies of e4 means an increased risk for AD in African-Americans. Everyone has two copies, or alleles, of the APOE gene, one inherited from the father and one from the mother. People with two e4 alleles are at greatest risk of AD. Their risk, which decreased with age, was highest if they were under age 69. People with just one e4 allele also had a significant risk if they were younger than 69 or older than 78.

The conclusion did not surprise the study's authors. Dr. Neill Graff-Radford, chair of the Department of Neurology at Mayo Clinic in Jacksonville says, "The more we've found out about Alzheimer's disease in African-Americans, or in any population, the more similarities there are. The pathology is identical; the areas of brain atrophy like the hippocampus are similar."

However, two notable, previous studies of e4 in African-Americans suggested that one e4 allele alone was not as important a risk factor for AD in African-Americans as in other groups. Graff-Radford says those studies did not include enough individuals under 70 years old. He says that was a problem, because e4 seems to confer the most risk for developing AD before people reach age 70. His group looked at e4 in 256 individuals 70 years old and younger. "The other strong point in our study was that it included several medical centers, and the risk was seen at all the centers that contributed a large enough population," Graff-Radford says. Dr. Floyd Willis, a Mayo Clinic physician and one of the study's authors, says the study ought to move researchers beyond debating whether e4 is a risk factor for Alzheimer's in African-Americans. Willis is interested in the distribution of e4 among the races and whether the disparity could indicate other important AD risk factors.

"If you look at e4 from people of different racial backgrounds, ordinarily you'd think the distribution should be similar. People are people," Willis says. "The fact of the matter is, the e4 frequency in Africans is significantly higher compared to African-Americans. And the level in African-Americans is again significantly higher than in Caucasians. So you might conclude that the more e4, the more Alzheimer's disease. But, the association is not that straightforward." There is a slightly higher incidence among African-Americans compared to white Americans but it hasn't been entirely explained by more e4 in the African-American population.

Willis suggests environment, diet or other diseases different in Africans and African-Americans may play a role in the development of AD independent of the APOE gene. "The bottom line is, blacks may have a higher e4 frequency, but that's not necessarily transferring directly to a higher incidence of Alzheimer's," Willis says. "Yet people believe African-Americans have a higher prevalence of Alzheimer's disease. If it's not due to e4, what's causing it? Is there something that's protecting African-Americans from the effects of e4, while something else, maybe high blood pressure or diabetes, is putting them at greater risk?" Willis says if researchers can solve that puzzle, the answer could be applicable to all races.

The result of this study leads Graff-Radford to a final observation. "If the pathology, areas of degeneration and risk factors such as APOE 4 are very similar in the races, then treatments would work across different populations and any therapeutic trial should be inclusive of all races."

The results of this multicenter study were reported in the journal Archives of Neurology, April 2002. Study authors included: Neill Graff-Radford, M.D., Floyd Willis, M.D., Michael Hutton, Ph.D., Jennifer Adamson, Ph.D., all from Mayo Clinic, Jacksonville, Fla.; Robert Green, M.D., Lindsay Farrer, Ph.D., Boston University School of Medicine, Boston, Mass.; Adrienne Cupples, Ph.D., Boston University School of Public Health, Boston, Mass.; Rodney Go, Ph.D., University of Alabama, Birmingham, Ala.; Timi Edeki, M.D., Ph.D., Patrick Griffith, M.D., Mary Williams, Ed.D., Yvonne Hipps, Ph.D., Morehouse School of Medicine, Atlanta, Ga.; David Bachman, M.D., Medical University of South Carolina, Charleston, S.C.; Jonathan Haines, Ph.D., Vanderbilt University School of Medicine, Nashville, Tenn.

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Media contact: Erik Kaldor (904) 953-2299

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