Anti-11[E]-pyroglutamate-modified amyloid ß antibodies cross-react with other pathological Aß species: relevance for immunotherapy.

ABSTRACT

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 Aß peptide bearing amino-terminal pyroglutamate at position 11 (AßN11(pE)). We identified two B-cell epitopes recognized by rabbit anti-AßN11(pE) polyclonal antibodies. Interestingly, rabbit anti-AßN11(pE) polyclonal antibodies bound also to full-length Aß1-42 and N-truncated/modified AßN3(pE), suggesting that the three peptides may share a common B-cell epitope. Importantly, rabbit anti-AßN11(pE) antibodies bound to naturally occurring Aß aggregates present in brain samples from AD patients. These results are potentially important for developing novel immunogens for targeting N-truncated/modified Aß 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 Aß, which is absent in N-amino truncated peptides.