Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules

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Abstract

β-Amyloid 42 (Aβ42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the Aβ42 aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used α-hemolysin (α-HL) pores to probe the different aggregation transition of Aβ42 in the presence of β-cyclodextrin (β-CD), a promoter of Aβ42 aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that β-CD and CR have opposite effects on the aggregation of Aβ42. Translocation events of the monomeric Aβ42 peptide were significantly lower in amplitude currents than protofilaments, and protofilaments were captured in the α-HL nanopore with a longer duration time. CR binds to Aβ42 and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, β-CD promotes the aggregation of Aβ42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological α-HL nanopore.

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