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

The Alzheimer's amyloid-beta (Abeta) peptide exists as a number of naturally occurring forms due to differential proteolytic processing of its precursor molecule. Many of the Abeta 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 Abeta 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 Abeta fibrils has also been investigated by TEM. The results show that a diverse range of Abeta peptides form fibrils and also bind Congo red. The ability of both Abeta 1-28 and Abeta 29-40 to form fibrils indicates that there are at least two fibril-forming domains within the full-length Abeta 1-40 sequence, the ability of many Abeta 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 Abeta 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 Abeta fibrils.