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

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

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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.
Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Department of Biology, The University of Texas at San Antonio (UTSA), San Antonio, TX, 78249, USA.


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.

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