Design of peptides that form amyloid-like fibrils capturing amyloid β1-42 peptides

Amyloid P-peptide (A beta) plays a critical role in Alzheimer's disease (AD). The monomeric state of A beta can self-assemble into oligomers, protofibrils, and amyloid fibrils. Since the fibrils and soluble oligomers are believed to be responsible for AD, the construction of molecules capable of capturing these species could prove valuable as a means of detecting these potentially toxic species and of providing information pertinent for designing drugs effective against AD. To this aim, we have designed short peptides with various hydrophobicities based on the sequence of A beta 14-23, which is a critical region for amyloid fibril formation. The binding of the designed peptides to A beta and the amplification of the formation of peptide amyloid-like fibrils coassembled with A beta are elucidated. A fluorescence assay utilizing thioflavin T, known to bind specifically to amyloid fibrils, revealed that two designed peptides (LF and VF, with the leucine and valine residues, respectively, in the hydrophobic core region) could form amyloid-like fibrils effectively by using mature A beta 1-42 fibrils as nuclei. Peptide LF also coassembled with soluble A beta oligomers into peptide fibrils. Various analyses, including immunostaining with gold nanoparticles, enzyme-linked immunosorbent assays, and size-exclusion chromatography, confirmed that the LF and VF peptides formed amyloid-like fibrils by capturing and incorporating A beta 1-42 aggregates into their peptide fibrils. In this system, small amounts of mature A beta 1-42 fibrils or soluble oligomers could be transformed into peptide fibrils and detected by amplifying the amyloid-like fibrils with the designed peptides.