Early-onset Alzheimer's disease in two Iranian families: a genetic study

Early-onset Alzheimer's disease (EOAD) represents less than 5% of all AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least three cases in three generations. Mutations in the amyloid precursor protein (APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause of EOAD.

We investigated the genotype of EOAD in two generations of two families with EOAD living in an Iranian village.

The polymerase chain reaction method was used to study the presenilin-1 and APP genes in 25 subjects of these generations.

A guanine-to-adenine transition in exon 17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717 was detected in 14 subjects including 6 patients with EOAD.

This mutation demonstrates the importance of γ-secretase, the necessity of early detection of patients with memory decline in the susceptible population and raising public awareness of consanguinity marriages.