title: Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains "hot spots" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The "hot spots" of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD.
authors.affiliation: National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY, USA. lmiller@bnl.gov
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Tejas P
authors.initials: TP
authors.lastname: Telivala
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzirotti
authors.forename: Judit
authors.initials: J
authors.lastname: Miklossy
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D003300:Copper / Q000032:analysis*; D003952:Diagnostic Imaging / Q000379:methods; D006801:Humans; D007501:Iron / Q000032:analysis; D058225:Plaque, Amyloid / Q000737:chemistry; D017510:Protein Folding; D011859:Radiography; D013052:Spectrometry, X-Ray Emission / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D017356:Synchrotrons; D015032:Zinc / Q000032:analysis*
chemical_list: D016229:Amyloid beta-Peptides; D003300:Copper; D007501:Iron; D015032:Zinc; D002118:Calcium