Synchrotron X-ray Fluorescence and FTIR Signatures for Amyloid Fibrillary and Nonfibrillary Plaques
Autor: | Margarita Carmona, Ester Aso, Jofre Seira, Isidre Ferrer, Josep Cladera, Elena Álvarez-Marimon, Hiram Castillo-Michel, Juan Reyes-Herrera, Núria Benseny-Cases |
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Rok vydání: | 2021 |
Předmět: |
In situ
Amyloid Physiology Cognitive Neuroscience Plaque Amyloid Peptide Biochemistry Glycosaminoglycan 03 medical and health sciences 0302 clinical medicine Lipid oxidation Alzheimer Disease Spectroscopy Fourier Transform Infrared medicine Humans Protein secondary structure 030304 developmental biology chemistry.chemical_classification 0303 health sciences Amyloid beta-Peptides Chemistry X-Rays Cell Biology General Medicine medicine.disease Biophysics Alzheimer's disease Infrared microscopy Synchrotrons 030217 neurology & neurosurgery |
Zdroj: | ACS Chemical Neuroscience. 12:1961-1971 |
ISSN: | 1948-7193 |
Popis: | Amyloid plaques are one of the principal hallmarks of Alzheimer's disease and are mainly composed of Aβ 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-μFTIR 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 β-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. |
Databáze: | OpenAIRE |
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