Comparative study on the conformational stability of human and murine amyloid β peptide

A hallmark of Alzheimer's disease (AD) is the amyloid β (Aβ) peptide fibril formation and deposition. The murine Aβ displays high sequence identity to its human counterpart, while it remains obscure why the former is less likely to aggregate with age and even in the presence of metal ions. With an attempt to elucidate the mechanism underlying the distinct aggregation properties of murine and human Aβ, molecular dynamics (MD) technique was used to perform parallel simulations on murine and human Aβ(1-42), and three single-point mutants, i.e., R5G, Y10F and H13R of human Aβ(1-42), respectively. Parallel MD simulations on murine and human Aβ(1-42) revealed that the conformational stability of murine Aβ(1-42) is comparable with that of human counterpart. The simulations on the three single-point mutants also indicated that the R5G, Y10F and H13R mutations affect little on the conformational stability of the peptide. Therefore, the non-occurrence of murine Aβ aggregation may not arise from the dynamic characters of the peptide. Although the result is negative, it advances our understanding on the pathogenesis of AD.