Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Winkler, K; Scharnagl, H; Tisljar, U; Hoschützky, H; Friedrich, I; Hoffmann, MM; Hüttinger, M; Wieland, H; März, W.
Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis.
J Lipid Res. 1999; 40(3):447-455
Doi: 10.1016/S0022-2275(20)32449-4
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Scharnagl Hubert
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- Abstract:
- The genetic polymorphism of apolipoprotein E (apoE) is associated with the age of onset and relative risk of Alzheimer's disease (AD). In contrast to apoE3, the wild type allele, apoE4 confers an increased risk of late-onset AD. We demonstrate that the beta-amyloid peptide isoforms Abeta (1-28), Abeta (1-40), and Abeta (1-43) compete for the cellular metabolism of apoE3 and apoE4 containing beta-very low density lipoproteins. An antibody raised against Abeta (1-28) cross-reacted with recombinant apoE. Epitope mapping revealed positive amino acid clusters as common epitopes of Abeta (13 through 17; HHQKL) and apoE (residues 144 through 148; LRKRL), both regions known to be heparin binding domains. Abeta in which amino acids 13 through 17 (HHQKL) were replaced by glycine (GGQGL) failed to compete with the cellular uptake of apoE enriched betaVLDL. These observations indicate that Abeta and apoE are taken up into cells by a common pathway involving heparan sulfate proteoglycans.
- Find related publications in this database (using NLM MeSH Indexing)
- Alzheimer Disease - metabolism
- Amino Acid Sequence -
- Amyloid beta-Peptides - immunology Amyloid beta-Peptides - metabolism
- Antibodies - metabolism
- Apolipoprotein E3 -
- Apolipoproteins E - genetics Apolipoproteins E - metabolism
- Binding, Competitive -
- Cross Reactions - immunology
- Endocytosis - physiology
- Epitope Mapping -
- Fibroblasts -
- Heparitin Sulfate - metabolism
- Humans -
- Lipoproteins, VLDL - metabolism
- Membrane Glycoproteins - metabolism
- Molecular Sequence Data -
- Peptide Fragments - immunology Peptide Fragments - metabolism Peptide Fragments - pharmacology
- Polymorphism, Genetic - genetics
- Receptors, Cell Surface - metabolism
- Risk Factors -
- Find related publications in this database (Keywords)
- A beta amyloid
- Alzheimer's disease
- apolipoprotein E
- heparin binding domain