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APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives

From the Department of Psychiatry and Behavioral Sciences (Drs. Steffens, Plassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.

Address correspondence and reprint requests to Dr. David C. Steffens, Duke University Medical Center, Box 3903, Durham, NC 27710.

OBJECTIVE: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives.

BACKGROUND: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins.

METHODS: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE 4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD.

RESULTS: Concordance among twins was associated with increased risk of AD among relatives (logrank test, ² = 12.558; p = 0.0004), and the presence of at least one APOE 4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, ² = 7.712; p = 0.0055).

CONCLUSIONS: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Key words: Apolipoprotein E—Twins—Family—AD

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