[Screening for mutations of the precursor of beta-amyloid protein in early forms of Alzheimer disease. French Study Group of Alzheimer Disease].

Genetic linkage studies suggest that Alzheimer's disease (AD) is genetically heterogeneous and that in several early onset families the disease locus is close to the amyloid precursor protein (APP) gene on chromosome 21. Recently, several mutations of APP gene have been described. We screened 100 sporadic and familial cases of early onset AD in order to determine the frequency of two of these mutations, APP 717 Val-->Ile and APP 713 Ala-->Val. The patients included fulfilled NINCDS-ADRDA criteria of probable AD and their age of onset was 60 or lower. Seventy-five cases were sporadic and 25 were familial with at least one first or second degree affected relative. None of our cases presented the mutations. Combined results allow to presume that the APP 717 Val-->Ile mutation accounts for less than 0.8% of all early onset AD, and 3.8 +/- 2.8% of familial cases. While the pathogenic effect of the APP 717 Val-->Ile mutation is established, this is not the case for the APP 713 Ala-->Val mutation. Searching for the APP 717 mutations in early-onset AD is fully justified, taking into account its consequences for genetic counselling.