Investigating the process of fibril formation of the Iowa mutant of the Alzheimer\u27s peptide

The purpose of this study is to determine how the length of the beta-amyloid peptide, the specific region of the peptide, and a single point mutation affect the behavior of Alzheimer’s beta-amyloid. The beta-amyloid peptide, which is a 40 residue peptide that has been implicated as a potential cause of Alzheimer’s disease, has been shown to undergo a fibrillization process that involves numerous intermediate stages. One of the intermediate stages has revealed a high neurotoxicity and is believed to be the cause of neurodegeneration associated with Alzheimer’s disease. Various point mutations of the beta-amyloid peptide are responsible for the many familial forms of Alzheimer’s. Although familial diseases account for only a small percentage of Alzheimer’s cases, the study of their behavior can elucidate the mechanism through which fibrillization occurs by determining how each mutation, and its location, affect fibrillization. For the Iowa mutation, residue 23 in the amyloid beta peptide is changed from aspartic acid to asparagine. Residue 23 bonds with residue 28, enabling the peptide to misfold. Although the Iowa mutant undergoes the same general fibrillization process as the wild type, it has a different kinetic profile. This study focuses on a smaller fragment of the beta-amyloid peptide, Aβ22-35, which encompasses the hair-pin turn and the beta-sheet region of the peptide after the hair-pin turn. The point mutation can affect the fibrillization, structure, kinetics, and solubility of the peptide relative to that of the wild type