Journal of Molecular Medicine

, Volume 82, Issue 10, pp 706–714 | Cite as

Antibodies from a DNA peptide vaccination decrease the brain amyloid burden in a mouse model of Alzheimer’s disease

  • Jan G. Schultz
  • Ulrich Salzer
  • M. Hasan Mohajeri
  • Daniel Franke
  • Jochen Heinrich
  • Jovan Pavlovic
  • M. Axel Wollmer
  • Roger M. Nitsch
  • Karin Moelling
Original Article

Abstract

The neuropathology of Alzheimer’s disease (AD) is characterized by the accumulation of amyloid peptide Aβ in the brain derived from proteolytic cleavage of the amyloid precursor protein (APP). Vaccination of mice with plasmid DNA coding for the human Aβ42 peptide together with low doses of preaggregated peptide induced antibodies with detectable titers after only 2 weeks. One serum was directed against the four aminoterminal amino acids DAEF and differs from previously described ones. Both immune sera and monoclonal antibodies solubilized preformed aggregates of Aβ42 in vitro and recognized amyloid plaques in brain sections of mice transgenic for human APP. Passive immunization of transgenic AD mice caused a significant and rapid reduction in brain amyloid plaques within 24 h. The combined DNA peptide vaccine may prove useful for active immunization with few inoculations and low peptide dose which may prevent the recently described inflammatory reactions in patients. The monoclonal antibodies are applicable for passive immunization studies and may lead to a therapy of AD.

Keywords

Alzheimer’s disease DNA vaccine Monoclonal antibodies 

Abbreviations

AD

Alzheimer’s disease

Amyloid-β

APP

Amyloid precursor protein

ELISA

Enzyme-linked immunosorbent assay

GM-CSF

Granulocyte-macrophage colony-stimulating factor

IL

Interleukin

SDS

Sodium dodecyl sulfate

tPA

Tissue-type plasminogen activator

Notes

Acknowledgements

We thank Silvia Karer for excellent technical assistance, Ruth Graeferath for help with the thioflavin binding assay, and Jay Tracy for help with the Aβ42 ELISA. One monoclonal antibody was provided by Evotec NeuroScience (Hamburg). This work was supported to R.M.N. by the Kanton Zürich, the NCCR Neural Plasticity and Regeneration, the EU-DIADEM program and the Stammbach Foundation.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jan G. Schultz
    • 1
  • Ulrich Salzer
    • 1
    • 3
  • M. Hasan Mohajeri
    • 2
  • Daniel Franke
    • 1
  • Jochen Heinrich
    • 1
  • Jovan Pavlovic
    • 1
  • M. Axel Wollmer
    • 2
  • Roger M. Nitsch
    • 2
  • Karin Moelling
    • 1
  1. 1.Institute of Medical VirologyUniversity of ZurichZurichSwitzerland
  2. 2.Division of Psychiatry ResearchUniversity of ZurichZurichSwitzerland
  3. 3.Division of Clinical ImmunologyUniversity of FreiburgFreiburgGermany

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