Processing of the beta-amyloid precursor protein carrying the familial, Dutch-type, and a novel recombinant...

Mutations within the beta-amyloid precursor protein (beta-APP) gene that cosegregate with early onset familial Alzheimer's disease (FAD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch-type (HCHWA-D) have been reported. The effects of these mutations on the products of both the non-amyloidogenic and potentially amyloidogenic processing pathways of the beta-APP protein were examined in stably transfected cells. Processing of these mutants appeared to be the same as wild-type. These results contrasted sharply to those observed with a mutation near the amino terminus of the beta-protein domain of beta-APP. This mutation resulted in a two-fold decrease of a potentially amyloidogenic 11 kDa peptide fragment. The data suggest that the FAD and HCHWA-D mutations have no effect on the formation of potentially amyloidogenic fragments in this cell system, possibly implicating an alternative mechanism for their effects.