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J Neurol Sci. 2006 May 15;244(1-2):151-8. Epub 2006 Mar 6.

Abeta42 gene vaccination reduces brain amyloid plaque burden in transgenic mice.

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Alzheimer's Diseases Center, Department of Neurology, University of Texas Southwestern Medical Center, 5323, Harry Hines, Dallas, 75390-9036, USA.



To demonstrate that in APPswe/PS1DeltaE9 transgenic mice, gene gun mediated Abeta42 gene vaccination elicits a high titer of anti-Abeta42 antibodies causal of a significant reduction of Abeta42 deposition in brain.


Gene gun immunization is conducted with transgenic mice using the Abeta42 gene in a bacterial plasmid with the pSP72-E3L-Abeta42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Abeta42 antibody levels in serum and Abeta42 levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release gamma-interferon. Immunofluorescence detection of Abeta42 plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software.


Gene gun vaccination with the Abeta42 gene resulted in high titers of anti-Abeta42 antibody production of the Th2-type. Levels of Abeta42 in treated transgenic mouse brain were reduced by 60-77.5%. The Mann-Whitney U-test P=0.0286.


We have developed a gene gun mediated Abeta42 gene vaccination method that is efficient to break host Abeta42 tolerance without using adjuvant and induces a Th2 immune response. Abeta42 gene vaccination significantly reduces the Abeta42 burden of the brain in treated APPswe/PS1DeltaE9 transgenic mice with no overlap between treated and control mice.

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