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阿尔茨海默病淀粉样蛋白核心中磁铁矿颗粒的高分辨率分析成像与电子全息术

High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer's disease.

作者信息

Plascencia-Villa Germán, Ponce Arturo, Collingwood Joanna F, Arellano-Jiménez M Josefina, Zhu Xiongwei, Rogers Jack T, Betancourt Israel, José-Yacamán Miguel, Perry George

机构信息

Department of Physics and Astronomy, The University of Texas at San Antonio (UTSA), San Antonio, TX, 78249, USA.

School of Engineering, University of Warwick, Coventry, CV4 7AL, UK.

出版信息

Sci Rep. 2016 Apr 28;6:24873. doi: 10.1038/srep24873.

Abstract

Abnormal accumulation of brain metals is a key feature of Alzheimer's disease (AD). Formation of amyloid-β plaque cores (APC) is related to interactions with biometals, especially Fe, Cu and Zn, but their particular structural associations and roles remain unclear. Using an integrative set of advanced transmission electron microscopy (TEM) techniques, including spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM), nano-beam electron diffraction, electron holography and analytical spectroscopy techniques (EDX and EELS), we demonstrate that Fe in APC is present as iron oxide (Fe3O4) magnetite nanoparticles. Here we show that Fe was accumulated primarily as nanostructured particles within APC, whereas Cu and Zn were distributed through the amyloid fibers. Remarkably, these highly organized crystalline magnetite nanostructures directly bound into fibrillar Aβ showed characteristic superparamagnetic responses with saturated magnetization with circular contours, as observed for the first time by off-axis electron holography of nanometer scale particles.

摘要

脑内金属异常蓄积是阿尔茨海默病(AD)的一个关键特征。淀粉样β蛋白斑块核心(APC)的形成与生物金属(尤其是铁、铜和锌)的相互作用有关,但其具体的结构关联和作用仍不清楚。我们使用了一套综合的先进透射电子显微镜(TEM)技术,包括球差校正扫描透射电子显微镜(Cs-STEM)、纳米束电子衍射、电子全息术和分析光谱技术(能量过滤X射线能谱法(EDX)和电子能量损失谱(EELS)),证明APC中的铁以氧化铁(Fe3O4)磁铁矿纳米颗粒的形式存在。我们在此表明,铁主要以纳米结构颗粒的形式在APC内蓄积,而铜和锌则分布于淀粉样纤维中。值得注意的是,这些高度有序的结晶磁铁矿纳米结构直接与纤维状Aβ结合,呈现出具有圆形轮廓的饱和磁化特征超顺磁响应,这是通过纳米级颗粒的离轴电子全息术首次观察到的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8895/4848473/ec2a0045d59d/srep24873-f1.jpg

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