FTIR SPECTROSCOPIC STUDIES ON HELICAL INTERMEDIATE STAGE DURING AGGREGATION PROCESS OF THE B-AMYLOID 11-28 FRAGMENT AND ITS VARIANTS

摘要

The amyloid β peptide (Aβ) is the major component of the amyloid plaques in the brains of Alzheimer's disease patients. Monomeric, physiological Aβ is benign, but by an unknown mechanism it becomes aggregated and neurotoxic. Recent evidence suggests that Aβ oligomers, not the final, insoluble fibril, constitute the main cause of Aβ neurotoxicity. Studying rare genetic cases associated with the early, familial Alzheimer's disease led to the hypothesis that familial AD mutations facilitate Aβ assembly into neurotoxic oligomers. Despite many studies on clinically relevant Aβ variants, the mechanisms by which the single mutations cause diseases with diverse pathological presentation are not fully understood. To shed some light on details of structural changes accompanying the initial stage of the aggregation process, we have studied the Aβ(11-28) fragment and its mutation-related variants using FTIR spectroscopy. Our recent CD and aggregation studies on this Aβ fragment proved it to be a good model for structural studies .