MISSENSE MUTATIONS IN THE CHROMOSOME-14 FAMILIAL ALZHEIMERS-DISEASE PRESENILIN-1 GENE

Mutations in the presenilin genes (PS-1 and PS-2) cause early onset au tosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy- documented familial AD kindreds were screened for mutations in PS-1, a nd seven different mutations were identified. Three of these were new mutations (G209V A426P, and E120D), two were previously reported mutat ions in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predi cted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is t he most C-terminal PS-1 mutation identified to date. (C) 1998 Wiley-Li ss, Inc.