Histidine state (deprotonated, neutral, and protonated) is considered an important factor influencing the structural properties and aggregation mechanisms in amyloid beta-peptides (A beta), which are associated with the pathogenesis of Alzheimer's disease. Understanding the structural properties and aggregation mechanisms is a great challenge because two forms (the N-epsilon-H or N-delta-H tautomer) can exist in the free neutral state of histidine. Here, replica exchange molecular dynamics simulation was performed to elucidate the changes in structure and the mechanism of aggregation influenced by tautomeric behaviors of histidine in A beta(1-40). Our results show that sheet-dominating conformations can be found in the His6(delta)-His13(delta)-His14(delta) (delta delta delta) isomer with significant antiparallel sheet structures between R5-D7 and L34-G38, as well as between L17-F20 and L34-G38, implying that a new aggregation mechanism may exist to promote the generation of oligomers and/or aggregates. This work fundamental tautomeric behaviors of neutral histidine in the process of aggregation. is helpful in understanding the fundamental tautomeric behaviors of neutral histidine in the process of aggregation.