Polymorphism of amyloid-β fibrils and its effects on human erythrocyte catalase binding

The Alzheimer's amyloid-beta (A beta) peptide exists as a number of naturally occurring forms due to differential proteolytic processing of its precursor molecule. Many of the A beta peptides of different lengths form fibrils in vitro, which often show polymorphisms in the fibril structure. This study presents a TEM based analysis of fibril formation by eighteen different A beta peptides ranging in length from 5 to 43 amino acids. Spectrophotometric analysis of Congo red binding to the fibrillar material has been assessed and the binding of human erythrocyte catalase (HEC) to A beta fibrils has also been investigated by TEM. The results show that a diverse range of A beta peptides form fibrils and also bind Congo red. The ability of both A beta 1-28 and A beta 29-40 to form fibrils indicates that there are at least two fibril-forming domains within the full-length A beta 1-40 sequence, the ability of many A beta peptides to form Congo red-binding aggregates suggests that there may be up to 4 possible aggregation promoting domains. The binding of HEC was limited to A beta forms containing residues 29-32. The differing capacities of fibrillar and ribbon-like structures may reflect the accessibility of the 29-32 region and suggest that HEC may be able to discriminate between different forms of A beta fibrils. (C) 2009 Elsevier Ltd. All rights reserved.