Objectives: To reexamine the association between the apolipoprotein E epsilon4 allele (APOE epsilon4) and familial Alzheimer disease (AD), and to search for novel genes that may be associated with susceptibility in Caribbean Hispanic families with a history of AD.
Methods: Families were identified in Caribbean Hispanic communities in the greater New York City area, the Dominican Republic, and Puerto Rico. Each family in the study cohort included at least 2 living relatives with a history of dementia. All family members underwent neuropsychological testing and medical and neurological examinations to establish the presence or absence of dementia and to specify the type of dementia.
Results: Over a 2(1/2)-year period, 203 families were identified. Of these, 19 families had at least 1 family member with onset of dementia before age 55 years, with 8 of the 19 families showing an association with a previously unreported presenilin mutation. Multiple cases of AD were identified in 29 families. Overall, there were 236 affected sibling pairs with AD available for analysis. The average age at onset was 74 years. The presence of APOE epsilon4 was strongly associated with AD.
Conclusions: Both early-onset and late-onset familial AD occur in Caribbean Hispanics. In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE epsilon4. Future attempts to identify additional susceptibility genes should consider the effects of APOE epsilon4.