NO FOUNDER EFFECT IN 3 NOVEL ALZHEIMERS-DISEASE FAMILIES WITH APP-717VAL-]ILE MUTATION

We sequenced exons 16 and 17 of the APP (amyloid precursor protein) ge ne in 18 unrelated French Alzheimer's disease (AD) patients. These pat ients had an onset before the age of 60 and belonged to families with autosomal dominant transmission of the disease. We detected the APP 71 7 Val-->Ile mutation in three out of 18 (16.6%) families. In these thr ee families, all affected subjects had the APOE 3/3 genotype, but thei r ages of onset ranged from 38 to 60 years, indicating that factors ot her than the APOE genotype influence age of onset. Analysis of two pol ymorphic loci adjacent to the APP gene showed that at least two indepe ndent mutational events had occurred within these pedigrees, in spite of their origin in the same region of France.