, Volume 82, Issue 10, pp 706-714
Date: 06 Jul 2004

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

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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.

J.G. Schultz, U. Salzer, and M.H. Mohajeri contributed equally to this manuscript