Competition of A beta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis

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 A beta (1-28), A beta (1-40), and A beta (1-43) compete for the cellular metabolism of apoE3 and apoE4 containing beta-very low density lipoproteins, An antibody raise d against A beta (1-28) cross-reacted with recombinant apoE, Epitope mappin g revealed positive amino acid clusters as common epitopes of A beta (13 th rough 17; HHQKL) and apoE (residues 144 through 148; LRKRL), both regions k nown to be heparin binding domains. A beta in which amino acids 13 through 17 (HHQKL) were replaced by glycine (GGQGL) failed to compete with the cell ular uptake of apoE enriched beta VLDL.jlr These observations indicate that A beta and apoE, are taken up into cells by a common pathway involving hep aran sulfate proteoglycans.-Winkler, K, H. Scharnagl, U. Tisljar, H. Hoschu tzky I. Friedrich, M. M. Hoffman, M. Huttinger; H. Wieland, and W. Marz. Co mpetition of A beta amyloid peptide and apolipoprotein E for receptor-media ted endocytosis.