Effects of the mutations Glu 22 to Gln and Ala 21 to Gly on the aggregation of a synthetic fragment of the Alzheimer's amyloid β/A4 peptide

Abstract

We assessed the fibrillogenic properties of synthetic peptides corresponding to residues 13–26 of β/A4 amyloid, containing either the normal sequence ( β 13–26) or the mutations Glu 22 to Gln ( β 13–26Q22) and Ala 21 to Gly ( β 13–26G21). The kinetics of aggregation were monitored at 37°C and pH 7.4 by measuring the amount of peptide remaining in solution, using reverse-phase high performance liquid chromatography. Negative stain electron microscopy revealed that all of the peptides formed fibrils. However, β 13–26Q22 showed greatly accelerated fibril formation compared to the other two. The results suggest that the Q22 mutation confers increased amyloidogenic properties on the β/A4 peptide, whereas the G21 mutation acts by a different pathogenic mechanism.