The R269H mutation in presenilin-1 presenting as late-onset autosomal dominant Alzheimer's disease

Two siblings fulfilling clinical diagnostic criteria for late-onset Alzheimer's disease (AD) are reported. The family history suggested a total of nine individuals affected with AD in three generations with autosomal dominant disease transmission. Neurogenetic testing of the proband revealed a mutation, R269H, in the presenilin-1 (PS1) gene. Late-onset AD may be associated with deterministic PS1 mutations; these should be sought when the family history suggests autosomal dominant disease transmission.