Soluble multimeric Alzheimer β(1–40) pre-amyloid complexes in dilute solution

Aqueous solutions of β(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 sedimentable and filterable structures with β-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 left right wave arrow multimer equilibrium may partly explain the divergence of biological consequences with respect to neurotoxicity.