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Abeta42 gene vaccine prevents Abeta42 deposition in brain of double transgenic mice


Year of Publication:
Contact PI Name:
Roger N. Rosenberg
Contact PI Affiliation:
Alzheimer’s Diseases Center, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Bao-Xi Qu, Qun Xiang, Liping Li, Stephen Albert Johnston, Linda S. Hynan
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
The Rudman Foundation
The Luttrell Foundation
Study Goal and Principal Findings:

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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Abeta42 Gene Vaccine
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported
Non Human Primate
Model Type:
Strain/Genetic Background:
Not Applicable

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
beta Amyloid Deposits
beta Amyloid Load
Activated Astrocytes
Brain-beta Amyloid Peptide 42
Plasma-beta Amyloid Peptide 42
Interferon (IFN) gamma
Interleukin 4 (IL-4)
Anti-beta Amyloid Antibody Titers
Antibody Target Specificity
T Cell Response
Interferon (IFN) gamma Production
T Cells
beta Amyloid Load
Glial Fibrillary Acidic Protein (GFAP)
Brain-beta Amyloid Deposits
Plasma-beta Amyloid Peptides
Target Engagement (Reduction beta Amyloid Peptides-Brain)