Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
- 2 October 1992
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 258 (5079), 126-129
- https://doi.org/10.1126/science.1439760
Abstract
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.Keywords
This publication has 30 references indexed in Scilit:
- Processing of the Amyloid Protein Precursor to Potentially Amyloidogenic DerivativesScience, 1992
- Potentially Amyloidogenic, Carboxyl-Terminal Derivatives of the Amyloid Protein PrecursorScience, 1992
- Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's diseaseJournal of Molecular Biology, 1991
- Soluble derivatives of the β amyloid protein precursor of Alzheimer's disease are labeled by antisera to the β amyloid proteinBiochemical and Biophysical Research Communications, 1989
- Validation of clinical diagnostic criteria for Alzheimer's diseaseAnnals of Neurology, 1988
- Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's DiseaseScience, 1987
- Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer LocusScience, 1987
- In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to alzheimer's disease β-proteinBiochemical and Biophysical Research Communications, 1986
- Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril proteinBiochemical and Biophysical Research Communications, 1984
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984