N-terminal truncated pyroglutamyl beta amyloid peptide Abetapy3-42 shows a faster aggregation kinetics than the full-length Abeta1-42.

We tested directly the differences in the aggregation kinetics of three important beta amyloid peptides, the full-length Abeta1-42, and the two N-terminal truncated and pyroglutamil modified Abetapy3-42 and Abetapy11-42 found in different relative concentrations in the brains in normal aging and in Alzheimer disease. By following the circular dichroism signal and the ThT fluorescence of the solution in phosphate buffer, we found substantially faster aggregation kinetics for Abetapy3-42. This behavior is due to the particular sequence of this peptide, which is also responsible for the specific oligomeric aggregation states, found by TEM, during the fibrillization process, which are very different from those of Abeta1-42, more prone to fibril formation. In addition, Abetapy3-42 is found here to have an inhibitory effect on Abeta1-42 fibrillogenesis, coherently with its known greater infective power. This is an indication of the important role of this peptide in the aggregation process of beta-peptides in Alzheimer disease. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 861-873, 2009.