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

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• 作者：Bao-Xi Qu ; Qun Xiang ; Liping Li ; Stephen Albert Johnston ; Linda S. Hynan ; Roger N. Rosenberg
• 关键词：AD Alzheimer's disease ; Abeta- Amyloid beta ; APPswe/PS1deltaE9- Amyloid precursor protein(Swedish mutation)/presenilin 1 deltaE9 mutation ; ELISPOT- Enzyme-linked immunosorbent spot ; nm-nanometer ; SPSS-Statistical Package for the Social Sciences
• 刊名：Journal of the Neurological Sciences
• 出版年：2007
• 期刊代码：178_0022510x
• 类别：med
• 出版时间：15 September 2007
• 卷：260
• 期：1-2
• 页码：204-213
• 文件大小：2029 K

摘要

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.