Basic & Clinical Medicine ›› 2025, Vol. 45 ›› Issue (7): 897-904.doi: 10.16352/j.issn.1001-6325.2025.07.0897

• Original Articles • Previous Articles     Next Articles

25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models

XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong*   

  1. Department of Pharmacology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2025-03-24 Revised:2025-04-25 Online:2025-07-05 Published:2025-06-24
  • Contact: *yanyongliu@ibms.pumc.edu.cn

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 constructed 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 vaccine 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 neuro-pathological changes. It may be used to treat AD.

Key words: Alzheimer′s disease, recombinant gene vaccine, 25-35, glucose-regulated protein 94 (GRP94), active immunity

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