MOLECULAR-GENETICS OF ALZHEIMERS-DISEASE IN ITALIAN FAMILIES

We screened 11 families From different regions of Italy by direct sequencing of exon 17 of the APP gene. Two unrelated families carried the APP(717) mutation segregating with the disease. These two families originate from two Italian regions which are considered genetically separate. Published studies have demonstrated the presence of the APP(717) Val --> Ile mutation in kindreds of British or Japanese origin with early onset familial Alzheimer's disease. These data suggest that the APP(717) mutation is not confined to islander families which may share common founders. From the molecular genetic point of view we also did linkage analysis. Several families, in fact, have not shown a linkage with chromosome 21 and the resolution of this dilemma required investigation of those pedigrees both with additional markers from chromosome 21 and with markers From other chromosomes.