Synchrotron X-ray Fluorescence and FTIR Signatures for Amyloid Fibrillary and Nonfibrillary Plaques
Synchrotron X-ray Fluorescence and FTIR Signatures for Amyloid Fibrillary and Nonfibrillary Plaques
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DOI：
10.1021/acschemneuro.1c00048
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发表时间：
2021-05-14
影响因子：
5
通讯作者：
Benseny-Cases, Nuria
中科院分区：
文献类型：
--
作者：
Alvarez-Marimon, Elena;Castillo-Michel, Hiram;Benseny-Cases, Nuria
淀粉样斑块是阿尔茨海默病的主要标志之一，主要由A β淀粉样肽以及其他组分如脂质、阳离子或糖胺聚糖组成。淀粉样肽聚集体的结构与肽的毒性有关，并且高度依赖于聚集条件和辅因子的存在。虽然目前认为无定形聚集体是无毒的，但已发现低聚物/颗粒状（无定形）聚集体是有毒的。在这项工作中，我们在原位分析了两种不同类型的淀粉样蛋白沉积在阿尔茨海默病晚期患者的皮层切片。通过结合SR-mu FTIR研究肽的二级结构和ThS荧光作为二级结构的指示剂，我们发现了两种类型的斑块：ThS阳性斑块在1630 cm（-1）处具有清晰的红外带，这将对应于斑块，而ThS阴性斑块显示出非纤维状β-折叠和无序聚集结构的混合物，这将对应于非斑块（具有增加的无序结构的斑块）。FTIR光谱的分析允许脂质氧化与非脂性斑块的存在相关。使用SR纳米XRF和XANES分析了两种类型的斑块的金属组成。结果表明，铁（主要是Fe ~（2+））在植物斑块中的富集程度高于非植物斑块。然而，在非生物性斑块中，已发现Fe 3+比Fe 2+占主导地位。不同类型的聚集形式和不同类型的斑块中发现的金属的不同组成的鉴定对于理解阿尔茨海默病的发展可能是至关重要的。
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.