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Flemish and Dutch mutations in amyloid beta precursor protein have different effects on amyloid beta secretion.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 1998 Oct; Vol. 5 (4), pp. 281-6. - Publication Year :
- 1998
-
Abstract
- Mutations in the amyloid beta precursor protein (APP) gene cosegregate with autosomal dominant Alzheimer disease (AD). Brain pathology of AD is characterized by amyloid deposition in senile plaques and by neurofibrillary tangles. Amyloid deposits in AD brains consist of amyloid beta (A beta), a 4-kDa proteolytic product of APP. In contrast, two other mutations in APP, the Flemish APP692 and Dutch APP693 mutations, are associated with autosomal dominant cerebral hemorrhages due to congophilic amyloid angiopathy (CAA) in the presence or absence of AD pathology, respectively. Both mutations are located within A beta near the constitutive cleavage site. While a common effect of AD-linked mutations is to elevate A beta 42 extracellular concentrations, not much is known about the effect of APP692 and APP693. Here we provide evidence that APP692 and APP693 have a different effect on A beta secretion as determined by cDNA transfection experiments. While APP692 upregulates both A beta 40 and A beta 42 secretion, APP693 does not. These data corroborate with previous findings that increased A beta secretion and particularly of A beta 42, is specific for AD pathology.
- Subjects :
- Amino Acid Sequence
Amyloid beta-Protein Precursor metabolism
Animals
CHO Cells cytology
CHO Cells metabolism
Cell Line
Cricetinae
DNA, Complementary genetics
Humans
Molecular Sequence Data
Mutation
Peptide Fragments metabolism
Plasmids genetics
Recombinant Fusion Proteins genetics
Transfection
Tumor Cells, Cultured cytology
Tumor Cells, Cultured metabolism
Amyloid beta-Peptides metabolism
Amyloid beta-Protein Precursor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0969-9961
- Volume :
- 5
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 9848098
- Full Text :
- https://doi.org/10.1006/nbdi.1998.0202