Familial aggregation in Alzheimer’s disease: Comparison of risk among relatives of early- and late-onset cases, and among male and female relatives in successive generations

Although the morbid risk of Alzheimer’s disease (AD) is increased among relatives of AD index cases, it is not yet clear whether the extent of familial aggregation is similar for probands of all ages, or for male and female relatives. The present study investigated the incidence of AD-like illness among 379 first-degree relatives of 79 probands in a continuing longitudinal study of AD. Cumulative incidence among relatives incread strikingly with age to 49% by age 87, and the risks observed did not differ appreciably among relatives of presenile-onset versus senile-onset probands. Risks were also similar among parents and sibs. Female relatives appeared to develop the disease earlier than males, but the age-specific risk curves for the two sexes did not differ significantly. These results should not be viewed as direct evidence for dominant genetic transmission of late-onset AD, but they suggest a rationale for formal genetic studies in late-onset (often apparently “sporadic”) disease as well as earlier-onset (“familial”) cases.