TY - JOUR
T1 - Aβ42 gene vaccine prevents Aβ42 deposition in brain of double transgenic mice
AU - Qu, Bao Xi
AU - Xiang, Qun
AU - Li, Liping
AU - Johnston, Stephen Albert
AU - Hynan, Linda S.
AU - Rosenberg, Roger N.
N1 - Funding Information:
This study was supported by P30AG12300 Alzheimer's Disease Center grant from the National Institutes of Health, National Institute on Aging, Bethesda, MD; U01 AG16976 the National Alzheimer's Coordinating Center grant, Seattle, WA.; Alzheimer's Association Research Grant, and the Rudman Foundation, Dallas, Texas; The Luttrell Foundation, Belmont, California and unrestricted funds to SAJ in the Biodesign Institute.
PY - 2007/9/15
Y1 - 2007/9/15
N2 - Aβ42 peptide aggregation and deposition is an important component of the neuropathology of Alzheimer's disease (AD). Gene-gun mediated gene vaccination targeting Aβ42 is a potential method to prevent and treat AD. APPswe/PS1ΔE9 transgenic (Tg) mice were immunized with an Aβ42 gene construct delivered by the gene gun. The vaccinated mice developed Th2 antibodies (IgG1) against Aβ42. The Aβ42 levels in brain were decreased by 41% and increased in plasma 43% in the vaccinated compared with control mice as assessed by ELISA analysis. Aβ42 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-Aβ42 antibody. These new findings advance significantly our knowledge that gene-gun mediated Aβ42 gene immunization effectively induces a Th2 immune response and reduces the Aβ42 levels in brain in APPswe/PS1ΔE9 mice. Aβ42 gene vaccination may be safe and efficient immunotherapy for AD.
AB - Aβ42 peptide aggregation and deposition is an important component of the neuropathology of Alzheimer's disease (AD). Gene-gun mediated gene vaccination targeting Aβ42 is a potential method to prevent and treat AD. APPswe/PS1ΔE9 transgenic (Tg) mice were immunized with an Aβ42 gene construct delivered by the gene gun. The vaccinated mice developed Th2 antibodies (IgG1) against Aβ42. The Aβ42 levels in brain were decreased by 41% and increased in plasma 43% in the vaccinated compared with control mice as assessed by ELISA analysis. Aβ42 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-Aβ42 antibody. These new findings advance significantly our knowledge that gene-gun mediated Aβ42 gene immunization effectively induces a Th2 immune response and reduces the Aβ42 levels in brain in APPswe/PS1ΔE9 mice. Aβ42 gene vaccination may be safe and efficient immunotherapy for AD.
KW - AD Alzheimer's disease
KW - APPswe/PS1deltaE9- Amyloid precursor protein(Swedish mutation)/presenilin 1 deltaE9 mutation
KW - Abeta- Amyloid beta
KW - ELISPOT- Enzyme-linked immunosorbent spot
KW - SPSS-Statistical Package for the Social Sciences
KW - nm-nanometer
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U2 - 10.1016/j.jns.2007.05.012
DO - 10.1016/j.jns.2007.05.012
M3 - Article
C2 - 17574274
AN - SCOPUS:34547688911
SN - 0022-510X
VL - 260
SP - 204
EP - 213
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -