Clements A,, Walsh, Williams, Allsop.
Effects of the mutations Glu22 to Gln and Ala21 to Gly on the aggregation of a synthetic fragment of the Alzheimer's amyloid b/A4 peptide.
Neurosci Lett. 1993 Oct;161(1):17-20.
We assessed the fibrillogenic properties of synthetic peptides corresponding to residues 13-26 of b/A4 amyloid, containing either the normal sequence (beta 13 26) or the mutations Glu22 to Gln (b 13-26Q22) and Ala21 to Gly (beta 13-26G21). The kinetics of aggregation were monitored at 37 degrees 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, b 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 b/A4 peptide, whereas the G21 mutation acts by a different pathogenic mechanism.