Simplified β-amyloid peptides for safer Alzheimer’s vaccines development

Abstract

Over the past few years, new ways of fighting Alzheimer’s disease have emerged based on stimulating the immunitary defence system of the patients. To avoid toxicity and autoimmune response related to the Aβ[1-42] peptide immunotherapy, in the last decade a large number of works aimed at identifying new classes of safe Aβ derivatives by modifying the full length β-amyloid form. In strict agreement with the purposes of the sequence-simplification technology, Aβ[1-16], Aβ[13-28] and Aβ[25-42] fragments were selected in order to retain the major immunogenic sites of the Aβ[1-42] peptide, and corresponding simplified forms were designed and synthesized. All glycinated Aβ derivatives showed immunogenic and antigenic properties similar to the parent Aβ[1-42] peptide, and raised antibodies were all able to cross-recognize both Aβ[1-42] and Aβ[1-40] synthetic structures. All Aβ simplified forms showed reduced fibrillogenic and inflammatory properties. In particular, the Aβ[13-28]+G form failed to induce IFN-γ production thus suggesting that this molecule could represent a good candidate for potentially safer AD vaccine therapy.