KCS

Modulating the formation process of amyloid-β fibril, especially kinetically delaying its early onset, is an applicable solution for Alzheimer's disease patients along with early diagnosis. The aggregates of Amyloid-β (Aβ) fibrils which are commonly observed in the brain of the Alzheimer's disease patients are considered to be closely related to the pathogenesis of the disease. Amyloid-β peptides with different number of residues may look alike but clearly have different physical properties. The peptides consisting of 40 and 42 amino acids, the two most dominant species, only differ in two amino acids of the N-terminal which is what provokes the difference of the entire morphology of their fibril structure, accelerated fibrillation of Aβ 42 to Aβ 40 as well as other properties. Since Aβ 42 to Aβ 40 ratio is found to be higher in patients compared to non-patients, we suggested the distinct physical properties of Aβ 42 to act as key factors in making it prone to self-assembly. In this study, we rationally designed mutant peptides with various point mutations based on their structure and physical properties. Designed mutant peptides have not only shown suppressed self-assembly, but also slowed down fibrillation process when mixed with wild type Amyloid-β (1-42).