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Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid-ß had distinct effects on neuropathology and cognitive deficits in EAE/AD mice.
Br J Pharmacol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034757


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 Aß1-42 aggregates (Aß42 vaccine) and an oligomer-specific conformational epitope (AOE1 vaccine), respectively.EXPERIMENTAL APPROACH: EAE/AD mice were immunized with the Aß42 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.


In contrast to previous findings in conventional AD animal models, Aß42 immunization promoted neuroinflammation, enhanced Aß levels and plaque burden, and failed to restore cognitive deficits in EAE/AD mice. By contrast, AOE1 immunization dramatically attenuated neuroinflammation, reduced Aß levels, and improved cognitive performance in EAE/AD mice.


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 Aß oligomers may be safe and show clinical benefit for AD treatment.





Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China