关键词: 关键词：霍乱毒素B亚单位, Aβ多肽抗体, 5XFAD小鼠, 阿尔茨海默病

Abstract: Objective To study the inhibition effect of anti-Aβ monoclonal antibody(IgG) conjugated with cholera toxin B subunit(CB) on brain Aβ burden in senile dementia mice. Methods IgG was conjugated with CB by improved sodium metaperiodate method. CB-IgG amount that accessed into the brain of mice was measured by indirect ELISA, which was also employed to measure IgG amount of brain different regions and blood sample after 3 hours of IgG administration. Transgenic mice were used to study the role of CB–IgG in inhibition of Aβ burden compared with IgG IN group, IgG IV group and wild type mice, after 14 weeks of IgG administration, Aβ level of brain was assessed by sandwich ELISA and Aβ deposits and senile plaques were observed by immunostaining. Results The trace of IgG in brain could be detected after 0.3 hours of CB–IgG intranasal administration and IgG amount achieved to peak at 3 hours when the amount of IgG in hippocampus was 10-fold higher in CB-IgG group than IgG IN group or IgG IV group (P<0.05),and IgG amount in brain was similar between IgG IN and IgG IV group. Compared with positive control group, the Aβ level of CB-IgG IN group was markedly reduced (P<0.05), percent Aβ load in hippocampus and cortex in CB-IgG IN group were both reduced by 80％. Conclusion CB-IgG treatment via intranasal was a promising approach that can effectively accessed into brain, and decrease Aβ deposits and senile plaques, which is more effective than the other way.

Key words: Key words Choleratoxin B subunit, Anti-amyloidβpeptide antibodies, 5XFAD mice, Alzheimer’s disease