Single Point Mutations Induce a Switch in the Molecular Mechanism of the Aggregation of the Alzheimer's Disease Associated Aβ42 Peptide

Single point mutations in the Alzheimer's disease associated A beta(42) peptide are found to alter significantly its neurotcodc properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in A beta(42) fibrils and are associated with a dramatic switch in the fibril dependent mechanism by which A beta(42) aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the A beta peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity.