Abeta42 gene vaccine prevents Abeta42 deposition in brain of double transgenic mice.
Abeta42 peptide aggregation and deposition is an important component of the neuropathology of Alzheimer's disease (AD). Gene-gun mediated gene vaccination targeting Abeta42 is a potential method to prevent and treat AD. APPswe/PS1DeltaE9 transgenic (Tg) mice were immunized with an Abeta42 gene construct delivered by the gene gun. The vaccinated mice developed Th2 antibodies (IgG1) against Abeta42. The Abeta42 levels in brain were decreased by 41% and increased in plasma 43% in the vaccinated compared with control mice as assessed by ELISA analysis. Abeta42 plaque deposits in cerebral cortex and hippocampus were reduced by 51% and 52%, respectively, as shown by quantitative immunolabeling. Glial cell activation was also significantly attenuated in vaccinated compared with control mice. One rhesus monkey was vaccinated and developed anti-Abeta42 antibody. These new findings advance significantly our knowledge that gene-gun mediated Abeta42 gene immunization effectively induces a Th2 immune response and reduces the Abeta42 levels in brain in APPswe/PS1DeltaE9 mice. Abeta42 gene vaccination may be safe and efficient immunotherapy for AD.
Qu
Bao-Xi
BX
Alzheimer's Disease Center, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9036, USA.
Xiang
Qun
Q
Li
Liping
L
Johnston
Stephen Albert
SA
Hynan
Linda S
LS
Rosenberg
Roger N
RN
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019470:Biolistics; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D005911:Gliosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007074:Immunoglobulin G / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D008253:Macaca mulatta; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)