AIMS: . To develop multi-modal imaging methods for high-resolution mapping of iron in neurodegenerative brain tissue. . To examine the magnetic properties of neurodegenerative tissue for the possible presence of anomalous magnetic iron oxides. . To examine the effects of biogenic, magnetic iron biominerals (primarily magnetite) on amyloid-beta aggregation in vitro. Research Design & Methods: The primary method for mapping iron distribution in tissue sections is via synchrotron x-ray scanning which will be conducted at Argonne National Laboratory. This technique will be used to identify iron anomalies eventually on a cellular level. And to compose composit images using a variety of imaing techniques. This work will enable correlation of iron anomalies and structural form to specific cellular and tissue structures for the first time. Examination of the magnetic properties of neurodegenerative tissue will be carried out pdmarily using Superconducting Quantum Interference Device (SQUID) magnetometry and Magnetic Force Microscopy (MFM). Using these methods the magnetic iron biominerals in the tissue will be characterized and compared to published data on non-pathologic and epileptic tissue samples. This will provide information on the relative abundance and type of magnetic iron biomineral present in the tissue and will help to either confirm or refute preliminary studies of nanoscale magnetic iron biominerals in Alzheimer's disease (AD) tissue. The effects of strong, local magnetic fields generated by nanoscale magnetic iron biominerals on amyloid-beta peptide aggregation rates will be examined using thioflavin-T assay and TEM imaging of peptide aggregates. Aggregation rates will be assessed in control solutions, solutions of peptide with coated magnetic nanoparticles and sham solutions containing the same concentrations of non-magnetic nanoparticles with the same size distribution and surface chemistry. Gla: FOREIGN GRANT: As the PI is a US citizen based at Keele University in the United Kingdom, the project will be administered through a foreign institution - Keele. The PI has considerable and unique experience in the analysis of magnetic iron biominerals in the brain (he has led all of the previous work described in this proposal) and is one of the few people in the wodd working in this field. The proposed project is highly interdisciplinary, incorporating aspects of biophysics, chemistry, neurobiology and biomedical engineering. The PI has a uniquely diverse background related to the proposed research, having worked in physics, chemistry and biomedical engineering departments and the UF Brain Institute since obtaining his PhD in 1991. He has published extensively in nanoscale magnetic iron biomineralization in the brain and his work has been featured by the media in such journals as Science,The Economist, Fact/Switzerland, The Los Angeles Times/Washington Post wire service as well as newspaper, radio and television coverage in six countries. The Pl's combination of skills and experience related to the research proposed here is unique and unavailable in the US.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SSS-X (20))
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Snyder, Stephen D
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University of Keele
United Kingdom
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Hautot, Dimitri; Pankhurst, Quentin A; Morris, Chris M et al. (2007) Preliminary observation of elevated levels of nanocrystalline iron oxide in the basal ganglia of neuroferritinopathy patients. Biochim Biophys Acta 1772:21-5