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Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid-beta had distinct effects on neuropathology and cognitive deficits in EAE/AD mice
Yu, Xiao-Lin; Zhu, Jie; Liu, Xiang-meng; Xu, Peng-xin; Zhang, Yue; Liu, Rui-tian
2020-03-20
Source PublicationBRITISH JOURNAL OF PHARMACOLOGY
ISSN0007-1188
Pages12
AbstractBackground and Purpose Immunotherapeutic intervention is one of the most promising strategies for the prevention and treatment of Alzheimer's disease (AD). Although they showed great success in AD mouse models, the clinical trials of many immune approaches failed due to low efficacy and safety. Thus, an animal model which can show the potential side effects of vaccines or antibodies is urgently needed. In this study, we generated EAE/AD mice by crossing APP/PS1 mice with experimental autoimmune encephalomyelitis (EAE) mice. We then investigated the efficacy and safety of two vaccines: the immunogens of which were A beta 1-42 aggregates (A beta 42 vaccine) and an oligomer-specific conformational epitope (AOE1 vaccine), respectively. Experimental Approach EAE/AD mice were immunized with the A beta 42 vaccine or AOE1 vaccine five times at biweekly intervals. After the final immunization, cognitive function was evaluated by the Morris water maze, Y maze, and object recognition tests. Neuropathological changes in the mouse brains were analysed by immunohistochemistry and ELISA. Key Results In contrast to previous findings in conventional AD animal models, A beta 42 immunization promoted neuroinflammation, enhanced A beta levels and plaque burden, and failed to restore cognitive deficits in EAE/AD mice. By contrast, AOE1 immunization dramatically attenuated neuroinflammation, reduced A beta levels, and improved cognitive performance in EAE/AD mice. Conclusion and Implications These results suggest that the EAE/AD mouse model can exhibit the potential side effects of AD immune approaches that conventional AD animal models fail to display. Furthermore, strategies specifically targeting A beta oligomers may be safe and show clinical benefit for AD treatment.
DOI10.1111/bph.15015
Language英语
WOS KeywordALZHEIMERS-DISEASE ; CONCISE GUIDE ; IMMUNIZATION ; OLIGOMERS ; IMMUNOTHERAPY ; MICROGLIA ; MODEL ; CNS ; NEUROINFLAMMATION ; CONTRIBUTES
Funding ProjectNational Science and Technology Major Projects of New Drugs[2018ZX09733001-001-008] ; National Natural Science Foundation of China[81971610]
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
Funding OrganizationNational Science and Technology Major Projects of New Drugs ; National Natural Science Foundation of China
WOS IDWOS:000520724900001
PublisherWILEY
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Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/39762
Collection中国科学院过程工程研究所
Corresponding AuthorLiu, Rui-tian
AffiliationChinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Yu, Xiao-Lin,Zhu, Jie,Liu, Xiang-meng,et al. Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid-beta had distinct effects on neuropathology and cognitive deficits in EAE/AD mice[J]. BRITISH JOURNAL OF PHARMACOLOGY,2020:12.
APA Yu, Xiao-Lin,Zhu, Jie,Liu, Xiang-meng,Xu, Peng-xin,Zhang, Yue,&Liu, Rui-tian.(2020).Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid-beta had distinct effects on neuropathology and cognitive deficits in EAE/AD mice.BRITISH JOURNAL OF PHARMACOLOGY,12.
MLA Yu, Xiao-Lin,et al."Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid-beta had distinct effects on neuropathology and cognitive deficits in EAE/AD mice".BRITISH JOURNAL OF PHARMACOLOGY (2020):12.
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