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.
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Abbreviations
- AD :
-
Alzheimer’s disease
- Aβ :
-
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
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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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J.G. Schultz, U. Salzer, and M.H. Mohajeri contributed equally to this manuscript
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Schultz, J.G., Salzer, U., Mohajeri, M.H. et al. Antibodies from a DNA peptide vaccination decrease the brain amyloid burden in a mouse model of Alzheimer’s disease. J Mol Med 82, 706–714 (2004). https://doi.org/10.1007/s00109-004-0570-z
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DOI: https://doi.org/10.1007/s00109-004-0570-z