A Founder Mutation in Presenilin 1 Causing Early-Onset Alzheimer Disease in Unrelated Caribbean Hispanic Families

Abstract

The frequency of Alzheimer disease (AD) is higher among Hispanics, particularly those from the Caribbean Islands, compared with non-Hispanic whites.^1-3Mutations in presenilin 1 are known to be responsible for a large proportion of familial early-onset AD^4-7 and are typically completely penetrant. Presenilin 1 mutations have been described in patients or families of Spanish origin,^8-12 but Caribbean Hispanic families typically have not been included in comprehensive studies of the genetic determinants of early-onset AD. We initiated a study of familial AD in Caribbean Hispanic families, noting several individuals who developed the disease before the age of 55 years. We hypothesized that a genetic variation in presenilin 1 or the amyloid precursor protein would be associated with AD in these families.