Aβ42 and Aβ40: similarities and differences

The abnormal accumulation of amyloid- (A) peptide in the brain is one of the most important hallmarks of Alzheimer's disease. A is an aggregation-prone and toxic polypeptide with 39-43 residues, derived from the amyloid precursor protein proteolysis process. According to the amyloid hypothesis, abnormal accumulation of A in the brain is the primary influence driving Alzheimer's disease pathologies. Among all kinds of A isoforms, A40 and A42 are believed to be the most important ones. Although these two kinds of A differ only in two amino acid residues, recent studies show that they differ significantly in their metabolism, physiological functions, toxicities, and aggregation mechanism. In this review, we mainly summarize the similarities and differences between A42 and A40, recent studies on selective inhibitors as well as probes will also be mentioned. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.