A New Amyloid-Like β-Aggregate with Amyloid Characteristics, Except Fibril Morphology

Amyloid plaques, formed from amyloid β (Aβ) peptides (mainly Aβ40 or Aβ42), are one of the most important pathological characteristics of Alzheimerʹs disease. Here, a single D-form proline substitution in the 40-amino-acid Aβ40 peptide can totally change the aggregation behavior of this peptide. The residue immediately preceding each glycine in Aβ40 (S8, V24, I32, and V36) was individually replaced by D-form proline (DPro). The resulting DP-G sequence (the DPro residue and the following Gly residue) was designed as a “structural clip” to force the formation of a bend in the peptide, as this sequence has been reported to be a strong promoter of β-hairpin formation. The mutant peptide with Val24-to-DPro substitution, named V24P, formed a new amyloid-like β-aggregate at high peptide concentration. The aggregate has most of the characteristics of amyloid fibrils, except fibril morphology. Moreover, the mutant peptide V24P, when mixed with Aβ40, can attenuate the cytotoxicity of Aβ40.