Synchrotron X-ray Fluorescence and FTIR Signatures for Amyloid Fibrillary and Nonfibrillary Plaques

Amyloid plaques are one of the principal hallmarks of Alzheimer's disease and are mainly composed of A beta amyloid peptides together with other components such as lipids, cations, or glycosaminoglycans. The structure of amyloid peptide's aggregates is related to the peptide toxicity and highly depends on the aggregation conditions and the presence of cofactors. While fibrillary aggregates are nowadays considered nontoxic, oligomeric/granular (nonfibrillary) aggregates have been found to be toxic. In this work we have characterized in situ two different types of amyloid deposits analyzing sections of the cortex of patients in advanced stages of Alzheimer disease. By combining SR-mu FTIR for the study of the secondary structure of the peptide and ThS fluorescence as an indicator of fibrillary structures, we found two types of plaques: ThS positive plaques with a clear infrared band at 1630 cm(-1) that would correspond to fibrillary plaques and ThS negative plaques showing a mixture of nonfibrillar beta-sheet and unordered aggregated structures that would correspond to the nonfibrillary plaques (plaques with increased unordered structure). The analysis of the FTIR spectra has allowed correlation of lipid oxidation with the presence of nonfibrillary plaques. The metal composition of the two types of plaques has been analyzed using SR-nano-XRF and XANES. The results have shown higher accumulation of iron (mainly Fe2+) in fibrillary plaques than in nonfibrillary ones. However, in nonfibrillary plaques Fe3+ has been found to predominate over Fe2+. The identification of different types of aggregated forms and the different composition of metals found in the different types of plaques could be of paramount importance for the understanding of the development of Alzheimer disease.

Automated summary

Amyloid plaques in the cortex of patients with advanced Alzheimer's disease have been characterized into two types: fibrillary plaques with iron accumulation mainly in Fe2+ form, and nonfibrillary plaques with a mixture of beta-sheet and unordered structures where Fe3+ predominates over Fe2+. This distinction in plaque types and metal composition could play a key role in understanding the progression of Alzheimer's disease.