Anti-11[E]-pyroglutamate-modified amyloid β antibodies cross-react with other pathological Aβ species: Relevance for immunotherapy
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- 作者：Roxanna Perez-Garmendia ; Vanessa Ibarra-Bracamontes ; Vitaly Vasilevko ; Jose Luna-Muñ ; oz ; Raul Mena ; Tzipe Govezensky ; Gonzalo Acero ; Karen Manoutcharian ; David H. Cribbs ; Goar Gevorkian
- 关键词：N-truncated amyloid beta (Aß ; ) peptide ; Alzheimer's disease immunotherapy ; Immunodominant epitope ; B cell epitope
- 刊名：Journal of Neuroimmunology
- 出版年：2010
- 出版时间：15 December 2010
- 年：2010
- 卷：229
- 期：1-2
- 页码：248-255
- 全文大小：1413 K
文摘
N-truncated/modified forms of amyloid beta (Aß) peptide are found in diffused and dense core plaques in Alzheimer's disease (AD) and Down's syndrome patients as well as animal models of AD, and represent highly desirable therapeutic targets. In the present study we have focused on N-truncated/modified Aβ peptide bearing amino-terminal pyroglutamate at position 11 (AβN11(pE)). We identified two B-cell epitopes recognized by rabbit anti-AβN11(pE) polyclonal antibodies. Interestingly, rabbit anti-AβN11(pE) polyclonal antibodies bound also to full-length Aβ1-42 and N-truncated/modified AβN3(pE), suggesting that the three peptides may share a common B-cell epitope. Importantly, rabbit anti-AβN11(pE) antibodies bound to naturally occurring Aβ aggregates present in brain samples from AD patients. These results are potentially important for developing novel immunogens for targeting N-truncated/modified Aβ aggregates as well, since the most commonly used immunogens in the majority of vaccine studies have been shown to induce antibodies that recognize the N-terminal immunodominant epitope (EFRH) of the full length Aβ, which is absent in N-amino truncated peptides.