Familial Alzheimer Disease Among Caribbean Hispanics

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Abstract
A FAMILY HISTORY of Alzheimer disease (AD) is one of the strongest risk factors for the disease. The lifetime risk of AD for family members of patients approaches 50% in some studies, which suggests an age-dependent autosomal dominant mode of inheritance.1,2 Mutations in genes on chromosomes 1, 14, and 21 are associated with familial early-onset AD, often with an autosomal dominant pattern of inheritance.3,4 However, these genes account for only 10% of all AD. The discovery that a polymorphism in the APOE (apolipoprotein E) gene on chromosome 19 was associated with susceptibility to both sporadic and familial late-onset AD5 led to the search for other potential susceptibility genes. Sites for potential susceptibility genes on chromosome 12 have been identified,6 and, more recently, sites on chromosome 10 have also been identified.7-9 Attempts to confirm the linkage between chromosome 12 and AD have been variable,10-12 and the association with α2-macroglobulin, a candidate gene in the area, has also been inconsistent.13-16 Familial AD may be the result of complex inheritance involving many genes with incomplete penetrance or a combination of genetic and environmental factors.