Multiple Antigenic Peptide System Coupled with Amyloid Beta Protein Epitopes As An Immunization Approach to Treat...

Latest studies suggest that Alzheimer's disease (AD) is one of the "four big killers" that threaten the health of the elderly. AD affects about 46 million people across the world, and there is a critical need for research on new therapies for treating AD. The purpose of the present study was to develop and evaluate immunogens to elicit antibodies against the formation of amyloid beta protein (Aβ), a pathological hallmark of AD, as a therapeutic strategy in AD. In this study, serial potential immunogenic epitopes were screened according to the Aβ sequence. The screened linear epitopes on the Aβ C-terminal fragment were coupled with either the carrier protein keyhole limpet hemocyanin (KLH) or the synthesized 4-branch peptide (MAP₄). MAP₄ immunogens could effectively elicit immunogenicity against Aβ_1-42 monomer and fiber in Balb/C mice. Furthermore, MAP₄ sera could also effectively inhibit the formation of the Aβ_1-42 fiber. Interestingly, one of the MAP₄ sera was able to depolymerize the Aβ_1-42 fibers that had aggregated. The monoclonal antibody, 1H7, was shown to inhibit the formation of Aβ_1-42 fiber. MAP₄ carrier may provide benefits over current immunization strategies, as it does not induce inflammation. In conclusion, the MAP₄-Aβ conjugates offer a promising approach for the development of a safe and effective AD vaccine.