Aβ 42 gene vaccination reduces brain amyloid plaque burden in transgenic mice

Abstract

Objective To demonstrate that in APPswe/PS1ΔE9 transgenic mice, gene gun mediated Aβ 42 gene vaccination elicits a high titer of anti-Aβ 42 antibodies causal of a significant reduction of Aβ 42 deposition in brain. Methods Gene gun immunization is conducted with transgenic mice using the Aβ 42 gene in a bacterial plasmid with the pSP72-E3L-Aβ 42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Aβ 42 antibody levels in serum and Aβ 42 levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release γ-interferon. Immunofluorescence detection of Aβ 42 plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software. Results Gene gun vaccination with the Aβ 42 gene resulted in high titers of anti-Aβ 42 antibody production of the Th2-type. Levels of Aβ 42 in treated transgenic mouse brain were reduced by 60–77.5%. The Mann–Whitney U-test P = 0.0286. Interpretation We have developed a gene gun mediated Aβ 42 gene vaccination method that is efficient to break host Aβ 42 tolerance without using adjuvant and induces a Th2 immune response. Aβ 42 gene vaccination significantly reduces the Aβ 42 burden of the brain in treated APPswe/PS1ΔE9 transgenic mice with no overlap between treated and control mice.