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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Qu
Baoxi
B
Alzheimer's Diseases Center, Department of Neurology, University of Texas Southwestern Medical Center, 5323, Harry Hines, Dallas, 75390-9036, USA.
Boyer
Philip J
PJ
Johnston
Stephen Albert
SA
Hynan
Linda S
LS
Rosenberg
Roger N
RN
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D019470:Biolistics / Q000379:methods*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D058225:Plaque, Amyloid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)