Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models
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-...
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| Format: | Article |
| Language: | zho |
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Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
2025-07-01
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| Series: | Jichu yixue yu linchuang |
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| Online Access: | https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-897.pdf |
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| author | XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong |
| author_facet | XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong |
| author_sort | XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b155b29ffcb24122a5ef9415a780b7f2 |
| institution | Kabale University |
| issn | 1001-6325 |
| language | zho |
| publishDate | 2025-07-01 |
| publisher | Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. |
| record_format | Article |
| series | Jichu yixue yu linchuang |
| spelling | doaj-art-b155b29ffcb24122a5ef9415a780b7f22025-08-20T03:29:57ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252025-07-0145789790410.16352/j.issn.1001-6325.2025.07.0897Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse modelsXIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong0Department of Pharmacology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, ChinaObjective 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.https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-897.pdfalzheimer′s disease|recombinant gene vaccine|aβ25-35|glucose-regulated protein 94 (grp94)|active immunity |
| spellingShingle | XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models Jichu yixue yu linchuang alzheimer′s disease|recombinant gene vaccine|aβ25-35|glucose-regulated protein 94 (grp94)|active immunity |
| title | Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models |
| title_full | Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models |
| title_fullStr | Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models |
| title_full_unstemmed | Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models |
| title_short | Aβ25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models |
| title_sort | aβ25 35 based recombinant gene vaccine effectively improves cognitive dysfunction in alzheimer s disease mouse models |
| topic | alzheimer′s disease|recombinant gene vaccine|aβ25-35|glucose-regulated protein 94 (grp94)|active immunity |
| url | https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-897.pdf |
| work_keys_str_mv | AT xiaofangyanliwenhuayangnanhuangweiliuyanyong ab2535basedrecombinantgenevaccineeffectivelyimprovescognitivedysfunctioninalzheimersdiseasemousemodels |