Anti-11[E]-pyroglutamate-modified amyloid β antibodies cross-react with other pathological Aβ species: Relevance for immunotherapy

N-truncated/modified forms of amyloid beta (A beta) 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 A beta peptide bearing amino-terminal pyroglutamate at position 11 (A beta N11(pE)). We identified two B-cell epitopes recognized by rabbit anti-A beta N11(pE) polyclonal antibodies. Interestingly, rabbit anti-A beta N11(pE) polyclonal antibodies bound also to full-length A beta 1-42 and N-truncated/modified A beta N3(pE), suggesting that the three peptides may share a common B-cell epitope. Importantly, rabbit anti-A beta N11(pE) antibodies bound to naturally occurring A beta aggregates present in brain samples from AD patients. These results are potentially important for developing novel immunogens for targeting N-truncated/modified A beta 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 A beta, which is absent in N-amino truncated peptides. (C) 2010 Elsevier B.V. All rights reserved.