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Pilot study of altered copper metabolism as a biomarker for early diagnosis of Alzheimer’s disease with 64CuCL2-PET/CT

      Background

      Copper is a trace element required for development and normal function of human brains. Emerging body of evidence suggests the role of copper in pathogenesis of Alzheimer’s disease. The aim of this study was to explore the potential of altered copper metabolism as a biomarker for early diagnosis of Alzheimer’s disease with positron emission tomography/computed tomography (PET/CT) using copper-64 chloride (64CuCl2) as a radioactive tracer (64CuCl2-PET/CT).

      Methods

      APPSWE transgenic mice (N=4, 14 weeks old,), a mouse model of Alzheimer’s disease, were subjected to PET/CT after intravenous injection of copper-64 chloride (64CuCl2) as a tracer, using a small animal PET/CT scanner. A group of wild type C57BL/6 mice (N=4, 13 weeks old) and another group of Atp7b -/- knockout mice (N=4, 6 to 7 weeks old), a mouse model of Wilson’s disease, were used as controls. PET quantitative analysis was performed to compare 64Cu uptake in the brains of the APPSWE transgenic mice with the 64Cu uptake in the brains of C57BL/6 and Atp7b-/-KO mice, respectively.

      Results

      Increased 64Cu uptake was detected in the brains of the APPSWE transgenic mice, compared with the 64Cu uptake in the brains of the C57BL/6 mice and the Atp7b-/- KO mice, respectively. In addition to increased 64Cu uptake in the cortex, large increase of 64Cu uptake was also detected in the regions of olfactory bulb and caudate of the APPSWE transgenic mice. Furthermore, cerebral 64Cu uptake in the brains of the Atp7b-/- KO mice was found to be lower than the cerebral 64Cu uptake in both the C57BL/6 mice and the APPSWE transgenic mice. Decrease of cerebral 64Cu uptake in the Atp7b-/- KO mice was likely secondary to metabolic trapping of 64Cu in the liver of Atp7b-/-KO mice as visualized on the PET/CT images.

      Conclusions

      Increased 64Cu uptake was detected in the brains of APPSWE transgenic mice, compared with the 64Cu uptake in the brains of C57BL/6 mice and Atp7b-/- KO mice, respectively. The findings support further investigation of altered copper metabolism as a biomarker for early diagnosis of Alzheimer’s disease with PET/CT using 64CuCl2 as a radioactive tracer (64CuCl2-PET/CT).
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