Early‐onset Alzheimer's disease with a presenilin‐1 mutation at the site corresponding to the volga German presenilin‐2 mutation

Abstract
We describe a new mutation causing Alzheimer's disease (AD) in presenilin‐1 (N135D) that is at the homologous site to the presenilin 2 mutation (N141I) in Volga German kindreds. The phenotype of PS1 N135D is an early‐onset (34–38 years) disease. The mutation forms part of, and extends, the α‐helical array of mutations in transmembrane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.