title: The interaction between apolipoprotein E and Alzheimer's amyloid beta-peptide is dependent on beta-peptide conformation.
abstract: An important feature of Alzheimer's disease (AD) is the cerebral deposition of amyloid. The main component of the amyloid is a 39-44-amino acid residue protein called amyloid beta (A beta), which also exists as a normal protein in biological fluids, known as soluble A beta. A major risk factor for late-onset AD is the inheritance of the apolipoprotein (apo) E4 isotype of apoE. How apoE is involved in the pathogenesis of AD is unclear; however, evidence exists for a direct apoE/A beta interaction. We and others have shown that apoE copurifies with A beta from AD amyloid plaques and that under certain in vitro conditions apoE promotes a beta-sheet structure in A beta peptides. Currently we document the high affinity binding of A beta peptides to both human recombinant apoE3 and -E4 with a KD of 20 nM. This interaction is greatly influenced by the conformational state of the A beta peptide used. Furthermore, we show that the fibril modulating effect of apoE is also influenced by the initial secondary structure of the A beta peptide. The preferential binding of apoE to A beta peptides with a beta-sheet conformation can in part explain the copurification of A beta and apoE from AD amyloid plaques.
authors.affiliation: Department of Neurology, New York University Medical Center, New York 10016, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Golabek
authors.forename: C
authors.initials: C
authors.lastname: Soto
authors.forename: T
authors.initials: T
authors.lastname: Vogel
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D002942:Circular Dichroism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments