MOLECULAR-GENETICS OF ALZHEIMERS-DISEASE IN ITALIAN FAMILIES

We screened 11 families From different regions of Italy by direct sequ encing of exon 17 of the APP gene. Two unrelated families carried the APP(717) mutation segregating with the disease. These two families ori ginate from two Italian regions which are considered genetically separ ate. Published studies have demonstrated the presence of the APP(717) Val --> Ile mutation in kindreds of British or Japanese origin with ea rly onset familial Alzheimer's disease. These data suggest that the AP P(717) mutation is not confined to islander families which may share c ommon founders. From the molecular genetic point of view we also did l inkage analysis. Several families, in fact, have not shown a linkage w ith chromosome 21 and the resolution of this dilemma required investig ation of those pedigrees both with additional markers from chromosome 21 and with markers From other chromosomes.