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Prevention of pathological change and cognitive degeneration of Tg2576 mice by inoculating Aβ1-15 vaccine

Bibliographic

Year of Publication:
2008
Contact PI Name:
Zhibin Yao
Contact PI Affiliation:
Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Co-Authors:
JinJia Hu, GuoYing Li, HuaQiao Wang, Xian Lin
Primary Reference (PubMED ID):
Funding Source:
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Social Development Project of Guangdong Province
Science and Technology Planning Project of Guangzhou
Study Goal and Principal Findings:

This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating the subunit fragment of Aβ vaccine. Thirty-two Tg2576 mice were randomly divided into four groups, each having eight mice: Group I, the control group, inoculated with adjuvants; Group II, the Aβ42 group, inoculated with Aβ42 vaccine; Group III, the Aβ1-15 group, inoculated with Aβ1-15 vaccine; and Group IV, the Aβ36-42 group, inoculated with Aβ36-42 vaccine. The titer of the serum antibody against Aβ42 (Group II) was significantly higher than that of the control group (Group I), and a low level of antibodies could be detected in the brain homogenate in the three vaccine-inoculated groups. Morris water maze test showed that the Aβ42 group, Aβ1-15 group and Aβ36-42 group were obviously improved compared with the control group. The cultured splenocytes sampled from each group were induced by Con A or their respective antigens, and the cell proliferation of the three vaccine-inoculated groups was significantly higher than that of the control group. In the Aβ42 group, IL2 and IFN-γ were relatively low and IL4 and IL10 were relatively high. By contrast, IL4 and IL10 were much higher in the Aβ1-15 group and IL2 and IFN-γ were much higher in the Aβ36-42 group. The immunohistochemical test showed a large number of senile plaques in the brain cortex and hippocampus of the mice in the control group, no senile plaque in the brain of the Aβ1-15 group and Aβ42 group mice, and a small number of senile plaques in the brain of the Aβ36-42 group mice. The results suggest that the subunit fragment of Aβ1-15 vaccine could prevent not only cognitive and behavioral degeneration but also Aβ deposition and formation of senile plaques in Tg2576 mice.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 1-15
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 36-42
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 1-42
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
Not Reported

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
Biomarkers
Dose
Formulation
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
Experiment Notes

Number of Premature Deaths: one mouse in the Aβ36-42 group died at the age of 11 months.

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Histopathology
beta Amyloid Deposits
Biochemical
Interferon (IFN) gamma
Interleukin 2 (IL-2)
Interleukin 4 (IL-4)
Interleukin 10 (IL-10)
Immunochemistry
Brain-beta Amyloid Deposits
Cell Biology
Cell Viability
Cell Proliferation
Cytokine Production
Immunology
Anti-beta Amyloid Antibody Titers
Interferon (IFN) gamma Production
Splenocyte Response
Pharmacodynamics
Target Engagement (Reduction beta Amyloid Deposits)
Toxicology
Body Weight
General Activity
General Behavior
General Health
Physical Appearance
Food Intake
Water Consumption
Organ Weight
Organ Histopathology