42 gene vaccination reduces brain amyloid plaque burden in transgenic mice

Baoxi Qu, Philip J. Boyer, Stephen Albert Johnston, Linda S. Hynan, Roger N. Rosenberg

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Objective: To demonstrate that in APPswe/PS1ΔE9 transgenic mice, gene gun mediated Aβ42 gene vaccination elicits a high titer of anti-Aβ42 antibodies causal of a significant reduction of Aβ42 deposition in brain. Methods: Gene gun immunization is conducted with transgenic mice using the Aβ42 gene in a bacterial plasmid with the pSP72-E3L-Aβ42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Aβ42 antibody levels in serum and Aβ42 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 Aβ42 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 Aβ42 gene resulted in high titers of anti-Aβ42 antibody production of the Th2-type. Levels of Aβ42 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 Aβ42 gene vaccination method that is efficient to break host Aβ42 tolerance without using adjuvant and induces a Th2 immune response. Aβ42 gene vaccination significantly reduces the Aβ42 burden of the brain in treated APPswe/PS1ΔE9 transgenic mice with no overlap between treated and control mice.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of the Neurological Sciences
Volume244
Issue number1-2
DOIs
StatePublished - May 15 2006

Keywords

  • Aβ gene vaccination
  • Brain amyloid plaque
  • Transgenic mice

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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