부산대학교 도서관

Summary Aggregation of the hyperphosphorylated protein tau into neurofibrillary tangles and neuropil threads is a hallmark of Alzheimer disease (AD). Identification and characterization of the epitopes recognized by anti-tau antibodies might shed light on the molecular mechanisms of AD pathogenesis. Here we report on the biochemical and structural characterization of a tau-specific monoclonal antibody CBTAU-24.1, which was isolated from the human memory B cell repertoire. Immunohistochemical staining with CBTAU-24.1 specifically detects pathological tau structures in AD brain samples. The crystal structure of CBTAU-24.1 Fab with a phosphorylated tau peptide revealed recognition of a unique epitope (Ser235-Leu243) in the tau proline-rich domain. Interestingly, the antibody can bind tau regardless of phosphorylation state of its epitope region and also recognizes both monomeric and paired helical filament tau irrespective of phosphorylation status. This human anti-tau antibody and its unique epitope may aid in development of diagnostics and/or therapeutic AD strategies. Graphical Abstract Highlights • A tau-specific antibody CBTAU-24.1 was isolated from human memory B cells • The CBTAU-24.1 crystal structure with a tau peptide identifies a unique tau epitope • CBTAU-24.1interacts with PHF-tau in neurofibrillary tangles and neuropil threads • CBTAU-24.1 recognizes tau irrespective of phosphorylation in its epitope Antibodies targeting the tau protein can be used in immunotherapy or as diagnostic tools in Alzheimer disease. Zhang et al. report the biochemical, functional, and structural characterization of a human anti-tau antibody. Antibody CBTAU-24.1 recognizes a unique epitope in the proline-rich domain of tau and specifically detects pathological tau structures. [ABSTRACT FROM AUTHOR]