Processing of the beta-amyloid precursor protein carrying the familial, Dutch-type, and a novel recombinant C-terminal mutation.
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.
CNS-Department of Biophysics and Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.
K M
KM
Felsenstein
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Lewis-Higgins
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins