title: Physical interaction of ApoE with amyloid precursor protein independent of the amyloid Abeta region in vitro.
abstract: Variation at the APOE gene locus has been shown to affect the risk for Alzheimer's disease. To gain deeper insight into the postulated apoE-mediated amyloid formation, we have characterized the three common apoE isoforms (apoE2, apoE3, and apoE4) regarding their binding to amyloid precursor protein (APP). We employed the yeast two-hybrid system and co-immunoprecipitation experiments in cell culture supernatants of COS-1 cells, ectopically expressing apoE isoforms and APP751 holoprotein or a COOH-terminal Abeta deletion mutant protein, designated APPtrunc. We found that all three apoE isoforms were able to bind APP751 holoprotein in an Abeta-independent fashion. The interacting domains could be mapped to the NH2 termini of APP (amino acids 1-207) and apoE (amino acids 1-191). As a functional consequence of this novel APP751 ectodomain-mediated apoE binding, the secretion of soluble APP751 is differentially affected by distinct apoE isoforms in vitro, suggesting a new "chaperon-like" mechanism by which apoE isoforms may modulate APP metabolism and consequently the risk for Alzheimer's disease.
authors.affiliation: Institute for Medical Biology and Human Genetics, University of Innsbruck, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Hass
authors.forename: F
authors.initials: F
authors.lastname: Fresser
authors.forename: S
authors.initials: S
authors.lastname: Köchl
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: G
authors.initials: G
authors.lastname: Utermann
authors.forename: G
authors.initials: G
authors.lastname: Baier
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D017931:DNA Primers; D011994:Recombinant Proteins