Immunogenic properties of amyloid beta oligomers

Journal of Biomedical Science

Aurelija Zvirbliene³  Vilmante Borutaite²  Ramune Morkuniene²  Gintaras Valincius¹  Rima Budvytyte¹  Rita Lasickiene³  Indre Dalgediene³ 

[1] Institute of Biochemistry, Vilnius University, Mokslininku str. 12, LT-08662, Vilnius, Lithuania;Institute of Neurosciences, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50009, Kaunas, Lithuania;Institute of Biotechnology, Vilnius University, V. Graiciuno str. 8, LT-02241, Vilnius, Lithuania

关键词: Epitope mapping;    Neurotoxic oligomers;    Immunogenicity;    Neurotoxicity;    Amyloid beta (Aβ);    Alzheimer’s disease (AD);   

Others  :  824280
DOI  :  10.1186/1423-0127-20-10

 received in 2012-10-26, accepted in 2013-02-19,  发布年份 2013

【 摘 要 】

Background

The central molecule in the pathogenesis of Alzheimer’s disease (AD) is believed to be a small-sized polypeptide – beta amyloid (Aβ) which has an ability to assemble spontaneously into oligomers. Various studies concerning therapeutic and prophylactic approaches for AD are based on the immunotherapy using antibodies against Aβ. It has been suggested that either active immunization with Aβ or passive immunization with anti-Aβ antibodies might help to prevent or reduce the symptoms of the disease. However, knowledge on the mechanisms of Aβ-induced immune response is rather limited. Previous research on Aβ1-42 oligomers in rat brain cultures showed that the neurotoxicity of these oligomers considerably depends on their size. In the current study, we evaluated the dependence of immunogenicity of Aβ1-42 oligomers on the size of oligomeric particles and identified the immunodominant epitopes of the oligomers.

Results

Mice were immunized with various Aβ1-42 oligomers. The analysis of serum antibodies revealed that small Aβ1-42 oligomers (1–2 nm in size) are highly immunogenic. They induced predominantly IgG2b and IgG2a responses. In contrast, larger Aβ1-42 oligomers and monomers induced weaker IgG response in immunized mice. The monoclonal antibody against 1–2 nm Aβ1-42 oligomers was generated and used for antigenic characterization of Aβ1-42 oligomers. Epitope mapping of both monoclonal and polyclonal antibodies demonstrated that the main immunodominant region of the 1–2 nm Aβ1-42 oligomers is located at the amino-terminus (N-terminus) of the peptide, between amino acids 1 and 19.

Conclusions

Small Aβ1-42 oligomers of size 1–2 nm induce the strongest immune response in mice. The N-terminus of Aβ1-42 oligomers represents an immunodominant region which indicates its surface localization and accessibility to the B cells. The results of the current study may be important for further development of Aβ-based vaccination and immunotherapy strategies.

【 授权许可】

   
2013 Dalgediene et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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