Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer's disease mouse models
10.16352/j.issn.1001-6325.2025.07.0897
- VernacularTitle:基于Aβ25-35表位重组基因疫苗能有效改善阿尔茨海默病模型小鼠认知功能障碍
- Author:
Fangyan XIAO
1
;
Wenhua LI
;
Nan YANG
;
Wei HUANG
;
Yanyong LIU
Author Information
1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 药理学系,北京 100005
- Keywords:
Alzheimer's disease;
recombinant gene vaccine;
Aβ25-35;
glucose-regulated protein 94(GRP94);
active immunity
- From:
Basic & Clinical Medicine
2025;45(7):897-904
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects of a newly constructed Aβ25-35-based recombinant gene vaccine for Alzheimer's disease(AD).Methods The pcDNA-Aβ25-35-GRP94 recombinant gene vaccine was con-structed using Aβ25-35 as the epitope and pcDNA3.1 plasmid as the vector.Early APP/PS1 double-transgenic mice were selected as experimental subjects,including the AD control group and the pcDNA-Aβ25-35-GRP94 immunized group for regular immunization.ELISA was performed to detect the titers and isotypes of Aβ-specific antibodies;Morris Water Maze(MWM)Test and Open-Field Test(OFT)were performed to determine the changes in both cognitive ability and mental state of mice;Immunohistochemistry was used to assess the effects of the vac-cine on both Aβ plaques and glial cells in the brains of AD mouse models;ELISA kit was used to evaluate the level of inflammatory factors(TNF-α,IL-1β)in the mouse brain.Results Compared with the AD control group,the pcDNA-Aβ25-35-GRP94 vaccine induced APP/PS1 mice to produce higher levels of Aβ specific antibodies(P<0.05),and mainly induced IgG1 antibodies(P<0.01).The vaccine significantly reduced Aβ plaques in the brain tissue(P<0.05)and effectively alleviated learning memory impairment in APP/PS1 mice(P<0.05)without causing mental behavioral abnormalities.Moreover,the vaccine inhibited the abnormal proliferation of glial cells(P<0.05)and did not cause obvious inflammatory reactions in the brain,suggesting the vaccine was safe and effective.Conclusions Early vaccination with a Aβ25-35-based recombinant gene vaccine can induce the formation of high level of Aβ specific antibodies,effectively alleviate the learning memory impairment of AD and related neu-ro-pathological changes.It may be used to treat AD.
