EARLY-ONSET ALZHEIMERS-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 preseni lin-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 transmem brane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.