Nanoparticle Scanners for the Identification of Key Sequences Involved in the Assembly and Disassembly of β-Amyloid Peptides

The aggregation of 0-amyloid peptides (A beta), implied in the development and progression of Alzheimer's disease, is driven by a complex set of intramolecular and intermolecular interactions involving both hydrophobic and polar residues. The key residues responsible for the forward assembling process may be different from those that should be targeted to disassemble already formed aggregates. Molecularly imprinted nanoparticle (MINP) receptors are reported in this work to strongly and selectively bind specific segments of A beta(40). Combined fluorescence spectroscopy, atomic force microscopy (AFM) imaging, and circular dichroism (CD) spectroscopy indicate that binding residues 21-30 near the loop region is most effective at inhibiting the aggregation of monomeric A040, but residues 11-20 that include the internal 0 strand closer to the N-terminal represent the best target for disaggregating already formed aggregates in the polymerization phase. Once the aggregation proceeds to the saturation phase, binding residues 1-10 has the largest effect on the disaggregation, likely because of the accessibility of these amino acids relative to others to the MINP receptors.

Automated summary

The aggregation of Aβ peptides in Alzheimer's disease involves complex interactions between hydrophobic and polar residues. Molecularly imprinted nanoparticle (MINP) receptors strongly bind specific segments of Aβ(40), inhibiting the aggregation of monomeric A040 through binding residues 21-30 near the loop region. Residues 11-20, including the internal 0 strand closer to the N-terminal, represent the best target for disaggregating already formed aggregates during the polymerization phase. Binding residues 1-10 have the greatest effect on disaggregation in the saturation phase.