Analysis of Interaction Characteristics Between Amyloid β and Lecanemab by HDX‐MS

Background Soluble amyloid-β (Aβ) aggregates including protofibrils (PFs) have been reported to be more toxic than insoluble fibrils. Recently, pharmaceutical antibodies targeting these soluble Aβ developed. The structural dynamics and heterogeneity of made it difficult analyze the characteristics tertiary structure. To investigate conformational recognition lecanemab aggregates, PFs their change upon binding lecanemab, an antibody with preferential protofibrils, were studied using hydrogen-deuterium exchange mass spectrometry (HDX-MS). Method (1-42) prepared in vitro. hydrogen/deuterium (H/D) status for monomeric (1-40) by HDX-MS phosphate buffered saline (PBS) explore regional dynamics. effects anti–Aβ PF on H/D basis antibody- interaction specificity against PFs. Result protected from throughout molecule (1-40), though N-terminal mid region still showed relatively higher Upon was also further addition region, its protection level (1-40). both regions is considered between lecanemab. Conclusion results indicate that has high flexibility region. suggested involved as well epitope formation expected, there are possibility binding. indicated combinational action modulation