High precision isotope measurements reveal poor control of copper metabolism in Parkinsonism

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable 65Cu isotope tracer. The analyses of blood serum 65Cu/63Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.