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 (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.
Perez-Garmendia
Roxanna
R
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Cuidad Universitaria, México DF, Mexico.
Ibarra-Bracamontes
Vanessa
V
Vasilevko
Vitaly
V
Luna-Muñoz
Jose
J
Mena
Raul
R
Govezensky
Tzipe
T
Acero
Gonzalo
G
Manoutcharian
Karen
K
Cribbs
David H
DH
Gevorkian
Goar
G
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018985:Epitopes, B-Lymphocyte / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000276:immunology*; D011817:Rabbits
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D018985:Epitopes, B-Lymphocyte; D011761:Pyrrolidonecarboxylic Acid