p3 peptide, a truncated form of Aβ devoid of synaptotoxic effect, does not assemble into soluble oligomers

Abstract 

In previously proposed models of Aβ soluble oligomers, the N-terminal domain Aβ_1–16, which is missing in p3 peptides, protects the hydrophobic core of the oligomers from the solvent. Without this N-terminal part, oligomers of p3 peptides would likely expose hydrophobic residues to water and would consequently be less stable. We thus suggest, based on theoretical and experimental results, that p3 peptides would have a low propensity to assemble into stable oligomers, evolving then directly to fibrillar aggregates. These properties may explain why p3 would be devoid of any impact on synaptic function and moreover, strengthen the hypothesis that Aβ oligomers are the principal synaptotoxic forms of Aβ peptides in Alzheimer disease.

Keywords: Alzheimer’s disease, Amyloid β-peptide, p3 peptide, Oligomeric toxic forms, Molecular models