Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects.
Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects.
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DOI：
10.1039/c7nr06794a
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发表时间：
2018-07-05
期刊：
影响因子：
6.7
通讯作者：
Telling ND
中科院分区：
文献类型：
--
作者：
Everett J ;Collingwood JF ;Tjendana-Tjhin V ;Brooks J ;Lermyte F ;Plascencia-Villa G ;Hands-Portman I ;Dobson J ;Perry G ;Telling ND
同步软x射线纳米成像和光谱显微镜显示阿尔茨海默病淀粉样斑块中铁和钙的生物矿化。大脑中生物金属代谢的改变是阿尔茨海默病的一个关键特征，生物金属与淀粉样蛋白-β的相互作用与淀粉样斑块的形成有关。富含铁的聚集体，包括混合价氧化铁磁铁矿的证据，与淀粉样斑块有关。在体外观察到，在淀粉样蛋白-β聚集的情况下，铁的化学还原增加可能发生在人脑淀粉样斑块形成的部位，为了验证这一假设，利用同步加速器x射线光谱显微镜，在人类阿尔茨海默病患者分离的淀粉样斑块核心中，研究了生物金属，特别是铁的纳米级分布和物理化学状态。原位x射线磁性圆二色性揭示了磁铁矿的存在：这一发现得到了氧化铁晶体形态的生物成因磁铁矿的体表观察的支持。结合化学探针和磁探针的x射线光谱显微镜的特殊灵敏度和特异性，可以增强氧化铁相的区分。这促进了富铁相和低氧化态相的发现和形成，类似于零价铁和磁铁矿。在两种不同的矿物形式中发现了隔离钙，这表明体内淀粉样斑块钙化的动态过程。铁氧化态的范围和对生物成因磁铁矿的直接观察为铁的化学还原与淀粉样斑块的形成有关的假设提供了无与伦比的支持。这些新发现提出了具有挑战性的问题，即淀粉样蛋白-β聚集、斑块形成和破坏金属稳态对阿尔茨海默病中观察到的氧化负担的相对影响。
Synchrotron soft X-ray nano-imaging and spectromicroscopy reveals iron and calcium biomineralization in Alzheimer's disease amyloid plaques. Altered metabolism of biometals in the brain is a key feature of Alzheimer's disease, and biometal interactions with amyloid-β are linked to amyloid plaque formation. Iron-rich aggregates, including evidence for the mixed-valence iron oxide magnetite, are associated with amyloid plaques. To test the hypothesis that increased chemical reduction of iron, as observed in vitro in the presence of aggregating amyloid-β, may occur at sites of amyloid plaque formation in the human brain, the nanoscale distribution and physicochemical states of biometals, particularly iron, were characterised in isolated amyloid plaque cores from human Alzheimer's disease cases using synchrotron X-ray spectromicroscopy. In situ X-ray magnetic circular dichroism revealed the presence of magnetite: a finding supported by ptychographic observation of an iron oxide crystal with the morphology of biogenic magnetite. The exceptional sensitivity and specificity of X-ray spectromicroscopy, combining chemical and magnetic probes, allowed enhanced differentiation of the iron oxides phases present. This facilitated the discovery and speciation of ferrous-rich phases and lower oxidation state phases resembling zero-valent iron as well as magnetite. Sequestered calcium was discovered in two distinct mineral forms suggesting a dynamic process of amyloid plaque calcification in vivo. The range of iron oxidation states present and the direct observation of biogenic magnetite provide unparalleled support for the hypothesis that chemical reduction of iron arises in conjunction with the formation of amyloid plaques. These new findings raise challenging questions about the relative impacts of amyloid-β aggregation, plaque formation, and disrupted metal homeostasis on the oxidative burden observed in Alzheimer's disease.
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影响因子：
9.7
作者：
Cosmidis, Julie;Benzerara, Karim;Bourdelle, Franck
通讯作者：
Bourdelle, Franck
DOI：
10.1098/rsif.2014.0165
发表时间：
2014-06-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Everett J;Céspedes E;Shelford LR;Exley C;Collingwood JF;Dobson J;van der Laan G;Jenkins CA;Arenholz E;Telling ND
通讯作者：
Telling ND
影响因子：
4
作者：
Gallagher, Joseph J.;Finnegan, Mary E.;Lynch, Marina A.
通讯作者：
Lynch, Marina A.
影响因子：
4.2
作者：
Dhenain, Marc;El Tayara, Nadine El Tannir;Delatour, Benoit
通讯作者：
Delatour, Benoit
影响因子：
12.7
作者：
GRUNDKEIQBAL, I;FLEMING, J;JOSHI, JG
通讯作者：
JOSHI, JG