EFFECTS OF THE MUTATIONS GLU22 TO GLN AND ALA21 TO GLY ON THE AGGREGATION OF A SYNTHETIC FRAGMENT OF THE ALZHEIMERS AMYLOID-BETA A4 PEPTIDE

We assessed the fibrillogenic properties of synthetic peptides corresp onding to residues 13-26 of beta/A4 amyloid, containing either the nor mal sequence (beta13 26) or the mutations Glu 22 to Gln (beta13 26Q22) and Ala21 to Gly (beta13 26G21). The kinetics of aggregation were mon itored at 37-degrees-C and pH 7.4 by measuring the amount of peptide r emaining in solution, using reverse-phase high performance liquid chro matography. Negative stain electron microscopy revealed that all of th e peptides formed fibrils. However, beta13 26Q22 showed greatly accele rated fibril formation compared to the other two. The results suggest that the Q22 mutation confers increased amyloidogenic properties on th e beta/A4 peptide, whereas the G21 mutation acts by a different pathog enic mechanism.