Sodium dodecyl sulfate-resistant complexes of Alzheimer's amyloid beta-peptide with the N-terminal, receptor binding domain of apolipoprotein E.
Immunocytochemical, biochemical, and molecular genetic studies indicate that apolipoprotein E (apoE) plays an important role in the process of amyloidogenesis-beta. However, there is still no clear translation of these data into the pathogenesis of amyloidosis-beta. Previous studies demonstrated sodium dodecyl sulfate (SDS)-resistant binding of apoE to the main component of Alzheimer's amyloid-A beta and modulation of A beta aggregation by apoE in vitro. To more closely characterize apoE-A beta interactions, we have studied the binding of thrombolytic fragments of apoE3 to A beta in vitro by using SDS-polyacrylamide gel electrophoresis and intrinsic fluorescence quenching. Here we demonstrate that SDS-resistant binding of A beta is mediated by the receptor-binding, N-terminal domain of apoE3. Under native conditions, both the N- and C-terminal domains of apoE3 bind A beta; however, the former does so with higher affinity. We propose that the modulation of A beta binding to the N-terminal domain of apoE is a potential therapeutic target for the treatment of amyloidosis-beta.
Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 USA. golabeck@popmail.med.nyu.edu
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Golabek
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Kida
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Walus
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Perez
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Wisniewski
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Soto
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40); D012967:Sodium Dodecyl Sulfate