3 DIFFERENT MUTATIONS OF PRESENILIN-1 GENE IN EARLY-ONSET ALZHEIMERS-DISEASE FAMILIES

Presenilin-1 (PS-1) gene of three Japanese pedigrees with early-onset familial Alzheimer's disease (FAD) disclosed two novel missense mutati ons resulting in Val96Phe and Ile213Thr, and one mutation resulting in His163Arg, The mean age at onset in a family with His163Arg mutation was similar to those reported in other families with His163Arg. Our re sults suggested the existence of a variety of PS-1 mutations, and that early-onset FAD with PS-1 mutations is highly penetrant and is only r arely subject to modulation by generic or environmental modifying fact ors.