Excessive Accumulations of Fe, Zn and Cu in the Neurons from an Alzheimer’s Disease Patient

Metallic elements are required in numerous essential biological processes of the human body. Transition metal elements like iron, zinc or copper bound to proteins (metalloproteins) perform a variety of complex biological functions as catalysts which regulate biochemical reactions and physiological functions in cells and organs. Published reports have been pointing out that excessive accumulation or a disequilibrium within the concentrations or distributions of these elements may affect cell functions up to the point of degeneration or cell death.1 Specifically, imbalances of trace metallic elements may be deeply related to neuronal cell death in several neurodegenerative disorders by promoting oxidative stress.2,3 The aim of our studies have been the investigation of the distribution, concentration and chemical state of trace metallic elements in the cells, in order to understand the role of these elements in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and Amyotrophic lateral sclerosis. To gain a broader understanding of the underlying behavior of these elements in the neurodegeneration process, samples derived from human, monkey and mouse specimens were studied. For carrying out the analyses of these experiments, X-ray fluorescence spectroscopy (XRF) and X-ray absorption near edge structure spectroscopy (XANES), both using synchrotron radiation (SR) microbeams were applied. Synchrotron radiation is an ideal X-ray source which provides continuous and high intensity photon energy. Wide energy tunability and high brightness and collimation are the main features of SR. This allows the investigation of trace metallic elements with a low detection limit (∼0.1 pg) and high spatial resolution. SR-XRF is used for identifying trace elements, as well as determining their distribution and concentration on a single cell level. On the other side, SR-XANES is sensitive to valence state, local atomic structure and chemical state of the elements of the samples. Futhermore, the non-invasive nature of XRF and XANES techniques allows further examinations of the biological samples a posteriori by complementary methods, e.g. histological observations by staining, rendering procedures like isolating or purifying, basically unnecessary.