Improved synaptic and cognitive function in aged 3 × Tg-AD mice with reduced amyloid-β after immunotherapy with a novel recombinant 6Aβ15-TF chimeric vaccine.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder impairing memory and cognition. In this study, we describe the immunogenicity and protective efficacy of the novel recombinant 6Aβ15-TF chimeric antigen as a subunit protein vaccine for AD. Recombinant 6Aβ15-TF chimeric vaccine induced strong Aβ-specific humoral immune responses without Aβ-specific T cell immunity in C57/BL6 and 3 × Tg-AD mice at different ages. As an early immunotherapy model for AD, this vaccine induced high titers of long-lasting anti-Aβ42 antibodies in aged 3 × Tg-AD mice, which led to improve behavioral performance and markedly reduced the levels of insoluble and soluble Aβ and Aβ oligomers. In agreement with these findings, immunotherapy with 6Aβ15-TF prevented the Aβ-induced decrease of presynaptic and postsynaptic proteins in aged 3 × Tg-AD mice. Our results suggest that this novel and highly immunogenic recombinant 6Aβ15-TF chimeric vaccine provides neuroprotection in AD mice and can be considered an effective AD candidate vaccine.