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

We describe a new mutation causing Alzheimer's disease (AD) in presenilin-1 ((ND)-D-135) that is at the homologons site to the presenilin 2 mutation ((NI)-I-141) in Volga German kindreds. The phenotype of PS1 (ND)-D-135 is an early-onset (34-38 years) disease. The mutation forms part of, and extends, the alpha-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.