First Author | Acero G | Year | 2020 |
Journal | Neurosci Lett | Volume | 724 |
Pages | 134876 | PubMed ID | 32114116 |
Mgi Jnum | J:289388 | Mgi Id | MGI:6432556 |
Doi | 10.1016/j.neulet.2020.134876 | Citation | Acero G, et al. (2020) Novel monoclonal antibody 3B8 specifically recognizes pyroglutamate-modified amyloid beta 3-42 peptide in brain of AD patients and 3xTg-AD transgenic mice. Neurosci Lett 724:134876 |
abstractText | In addition to the full-length beta-amyloid peptides (Abeta 1-40/42), several Abeta variants, truncated at their N- or C-termini and bearing different post-translational modifications, have been detected in the brain of Alzheimer s disease (AD) patients. AbetaN3(pE), an Abeta peptide bearing an amino-terminal pyroglutamate at position 3, is a significant constituent of intracellular, extracellular and vascular Abeta deposits in brain tissue from individuals with AD and Down syndrome. Pioneering immunotherapy studies have primarily focused on the full-length Abeta peptide, disregarding the presence of N-truncated/modified species. However, in recent years, increasing attention has been directed towards AbetaN3(pE), in both pre-clinical studies and clinical trials. In the present study, we generated and characterized an anti-AbetaN3(pE) mouse monoclonal antibody (3B8) that recognizes amyloid aggregates in brain tissue from AD patients and in 3xTg-AD transgenic mice. To identify the epitope recognized by 3B8, a library of random heptapeptides fused to the minor coat protein of M13 phage was screened. Results from screening, along with those from ELISA assays against distinct Abeta fragments, suggest recognition of two conformational epitopes present in AbetaN3(pE) and Abeta 3-42, regardless of the glutamate-pyroglutamate modification. The novel 3B8 antibody may be useful in future therapeutic and diagnostic applications for AD. |