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

Bao Xi Qu, Qun Xiang, Liping Li, Stephen Johnston, Linda S. Hynan, Roger N. Rosenberg

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

42 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.

Original languageEnglish (US)
Pages (from-to)204-213
Number of pages10
JournalJournal of the Neurological Sciences
Volume260
Issue number1-2
DOIs
StatePublished - Sep 15 2007

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Transgenic Mice
Vaccines
Firearms
Brain
Genes
Alzheimer Disease
Vaccination
Gene Targeting
Macaca mulatta
Neuroglia
Cerebral Cortex
Immunotherapy
Anti-Idiotypic Antibodies
Immunization
Hippocampus
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Antibodies

Keywords

  • Abeta- Amyloid beta
  • AD Alzheimer's disease
  • 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

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

42 gene vaccine prevents Aβ42 deposition in brain of double transgenic mice. / Qu, Bao Xi; Xiang, Qun; Li, Liping; Johnston, Stephen; Hynan, Linda S.; Rosenberg, Roger N.

In: Journal of the Neurological Sciences, Vol. 260, No. 1-2, 15.09.2007, p. 204-213.

Research output: Contribution to journalArticle

Qu, Bao Xi ; Xiang, Qun ; Li, Liping ; Johnston, Stephen ; Hynan, Linda S. ; Rosenberg, Roger N. / 42 gene vaccine prevents Aβ42 deposition in brain of double transgenic mice. In: Journal of the Neurological Sciences. 2007 ; Vol. 260, No. 1-2. pp. 204-213.
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