Original Article

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

Correspondence to: Karl Winkler

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 ß-amyloid peptide isoforms Aß (1–28), Aß (1–40), and Aß (1–43) compete for the cellular metabolism of apoE3 and apoE4 containing ß-very low density lipoproteins. An antibody raised against Aß (1–28) cross-reacted with recombinant apoE. Epitope mapping revealed positive amino acid clusters as common epitopes of Aß (13 through 17; HHQKL) and apoE (residues 144 through 148; LRKRL), both regions known to be heparin binding domains. Aß in which amino acids 13 through 17 (HHQKL) were replaced by glycine (GGQGL) failed to compete with the cellular uptake of apoE enriched ßVLDL.

These observations indicate that Aß and apoE are taken up into cells by a common pathway involving heparan sulfate proteoglycans.—Winkler, K., H. Scharnagl, U. Tisljar, H. Hoschützky, I. Friedrich, M. M. Hoffman, M. Hüttinger, H. Wieland, and W. März. Competition of Aß amyloid peptide and apolipoprotein E for receptor-mediated endocytosis. J. Lipid Res. 1999. 40: 447–455.

Supplementary key words: Aß amyloid, Alzheimer's disease, apolipoprotein E, heparin binding domain

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