Aβ₄₂ gene vaccine prevents Aβ₄₂ deposition in brain of double transgenic mice

Aβ₄₂ peptide aggregation and deposition is an important component of the neuropathology of Alzheimer's disease (AD). Gene-gun mediated gene vaccination targeting Aβ₄₂ is a potential method to prevent and treat AD. APPswe/PS1ΔE9 transgenic (Tg) mice were immunized with an Aβ₄₂ gene construct delivered by the gene gun. The vaccinated mice developed Th2 antibodies (IgG1) against Aβ₄₂. The Aβ₄₂ levels in brain were decreased by 41% and increased in plasma 43% in the vaccinated compared with control mice as assessed by ELISA analysis. Aβ₄₂ 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-Aβ₄₂ antibody. These new findings advance significantly our knowledge that gene-gun mediated Aβ₄₂ gene immunization effectively induces a Th2 immune response and reduces the Aβ₄₂ levels in brain in APPswe/PS1ΔE9 mice. Aβ₄₂ gene vaccination may be safe and efficient immunotherapy for AD.