Soluble multimeric Alzheimer beta(1-40) pre-amyloid complexes in dilute solution.
Aqueous solutions of beta(1-40) peptide spontaneously associate to form pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic conditions of pH and high peptide concentration these aggregates can further associate to form pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic conditions of pH and high peptide concentration these aggregates can further associate to form sedimentable and filterable structures with beta-sheet amyloid characteristics of Thioflavine T fluorescence. The presence of such preamyloid structures at low peptide concentration suggests a mechanism by which amyloid plaques can accrete additional material by a cooperative rather than monomeric growth. The existence of a monomer<==>multimer equilibrium may partly explain the divergence of biological consequences with respect to neurotoxicity.
Levine
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Department of Neurodegenerative Diseases, Parke-Davis Pharmaceutical Research Division of the Warner-Lambert Company, Ann Arbor, MI 48106-1047, USA.
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005976:Glutaral / Q000494:pharmacology; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry*; D011108:Polymers; D012995:Solubility; D012996:Solutions
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003432:Cross-Linking Reagents; D010446:Peptide Fragments; D011108:Polymers; D012996:Solutions; C078592:amyloid beta-protein (1-40); D005976:Glutaral