Altered cleavage and secretion of a recombinant β–APP bearing the Swedish familial Alzheimer's disease mutation
- 1 March 1994
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 6 (3) , 251-256
- https://doi.org/10.1038/ng0394-251
Abstract
Mutations within the β–amyloid precursor protein gene cosegregate with the early–onset form of familial Alzheimer's Disease (FAD). It is not known how these mutations result in disease; however, one early–onset AD mutation in a Swedish kindred increases potentially amyloidogenic fragments and β–protein production in cells expressing the mutant β–APP. Using a novel recombinant reporter system we found a qualitative change in the secreted product, from cleavage within the β–protein sequence to cleavage near the N–terminal region of the β–protein, even though the total amount of secreted mutant product is similar to wild–type. The results suggest that the increased formation of potentially amyloidogenic fragments in cells expressing the Swedish FAD occurs by enzymatic cleavage in the secretory pathway. Alterations in the secretory process may predispose an individual to AD.Keywords
This publication has 32 references indexed in Scilit:
- Processing of the β-amyloid precursor protein carrying the familial, Dutch-type, and a novel recombinant C-terminal mutationNeuroscience Letters, 1993
- Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein productionNature, 1992
- A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloidNature Genetics, 1992
- A mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's DiseaseScience, 1991
- Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein geneNature, 1991
- Amyloid precursor protein gene mutation in early-onset Alzheimer's diseaseThe Lancet, 1991
- Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's diseaseThe Lancet, 1991
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991
- Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch TypeScience, 1990
- The Genetic Defect Causing Familial Alzheimer's Disease Maps on Chromosome 21Science, 1987