Three-Dimensional Tomographic Imaging and Characterization of Iron Compounds within Alzheimer's Plaque Core Material

Article type: Research Article

Authors: Collingwood, Joanna F.^a | Chong, Ryan K. K.^b | Kasama, Takeshi^{b; c} | Cervera-Gontard, Lionel^b | Dunin-Borkowski, Rafal E.^{b; c; d} | Perry, George^{e; f} | Pósfai, Mihály^g | Siedlak, Sandra L.^e | Simpson, Edward T.^b | Smith, Mark A.^e | Dobson, Jon^{a; *}

Affiliations: [a] Institute of Science and Technology in Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, ST4 7QB, UK | [b] Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2, 3QZ, UK | [c] Frontier Research System, The Institute of Physical and Chemical Research, Hatoyama, Saitama 350-0395, Japan | [d] Center for Electron Nanoscopy, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark | [e] Department of Pathology, Case Western Reserve University, Cleveland Ohio, USA | [f] College of Sciences, University of Texas at San Antonio, San Antonio, Texas, USA | [g] Department of Earth and Environmental Sciences, University of Veszprém, POB 158, H-8201, Hungary

Correspondence: [*] Corresponding author: Jon Dobson, Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, ST4 7QB, United Kingdom. Tel.: +44 1782 554 253; Fax: +44 1782 717 079; E-mail: bea22@keele.ac.uk.

Note: [] Handling editor: Ralph Martins

Abstract: Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material – a hallmark of Alzheimer's disease pathology – in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain.

Keywords: Alzheimer's disease, amyloid, electron microscopy, ferritin, imaging, iron, magnetite, senile plaque core, tomography

DOI: 10.3233/JAD-2008-14211

Journal: Journal of Alzheimer's Disease, vol. 14, no. 2, pp. 235-245, 2008