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. Metal ions of zinc (Zn), copper (Cu), and iron (Fe) are present in the brain under normal conditions, but in AD it is thought that metal imbalances contribute to A¿ aggregation leading to oxidative damage and neuron degeneration. The hippocampus, a critical region affected by AD, has shown evidence of metal imbalance in AD. For example, Deibel and colleagues [3] found a decrease in Cu, and an increase in Zn and Fe in the hippocampus in AD. In addition, elevated expression of Zn transporter proteins ZnT3, ZnT4, and ZnT6 have been observed in the hippocampi of human AD patients and transgenic mice. Though metal homeostasis in the hippocampus appears to be critical in AD, how metal content in specific regions of the hippocampus changes over time remains to be determined. Thus, we examined the Cu, Fe, and Zn content the hippocampus of the PSAPP mouse model of AD (N = 20) and in control (CNT, N = 20) mice as a function of age using XRF microprobe. We hypothesized that PSAPP mice will show changes in hippocampal metal ion content as the mice age, while the content in CNT mice will remain constant.