METAL IONS AND PROTEIN STRUCTURE IN ALZHEIMER'S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease (AD) is a neurodegenerative disease that involves the misfolding of a normal protein  called Abeta  in the brain, which has recently been associated with the binding of metal ions. It is thought that metal imbalance is involved in protein misfolding and leads to oxidative damage and neuron degeneration. Yet, the functions of these metal ions and the misfolded proteins in the disease process are not well understood. Recently, we examined human brain tissue from severe AD cases using x-ray fluorescence (XRF) microprobe and found that AD tissue contains "hot spots" of zinc and copper. We also used synchrotron FTIR micro-spectroscopy to image the secondary structure of the misfolded Abeta protein. Interestingly, these hot spots are co-localized with Abeta "amyloid plaques", indicating an association of metal ions with amyloid formation in AD. However, the role of plaque formation and metal accumulation in the pathology of AD as the disease progresses is still not clear.