Aβ 42 gene vaccine prevents Aβ 42 deposition in brain of double transgenic mice

Abstract

Aβ 42 peptide aggregation and deposition is an important component of the neuropathology of Alzheimer's disease (AD). Gene-gun mediated gene vaccination targeting Aβ 42 is a potential method to prevent and treat AD. APPswe/PS1ΔE9 transgenic (Tg) mice were immunized with an Aβ 42 gene construct delivered by the gene gun. The vaccinated mice developed Th2 antibodies (IgG1) against Aβ 42. The Aβ 42 levels in brain were decreased by 41% and increased in plasma 43% in the vaccinated compared with control mice as assessed by ELISA analysis. Aβ 42 plaque deposits in cerebral cortex and hippocampus were reduced by 51% and 52%, respectively, as shown by quantitative immunolabeling. Glial cell activation was also significantly attenuated in vaccinated compared with control mice. One rhesus monkey was vaccinated and developed anti-Aβ 42 antibody. These new findings advance significantly our knowledge that gene-gun mediated Aβ 42 gene immunization effectively induces a Th2 immune response and reduces the Aβ 42 levels in brain in APPswe/PS1ΔE9 mice. Aβ 42 gene vaccination may be safe and efficient immunotherapy for AD.