Brain metal accumulation in Wilson's disease

Introduction: Brain metal accumulation is suggested in the pathogenesis of numerous neurodegenerative disorders. In Wilson's disease (WD), only copper has been examined. The aim of the present study was to evaluate the copper, iron, manganese, and zinc concentrations in autopsy tissue samples from the brains of WD patients.

Methods: The study material consisted of 17 brains (12 WD patients, 5 controls) obtained at autopsy. Samples were taken from four different regions of each brain: frontal cortex, putamen, pons, and nucleus dentatus. The copper, manganese, and zinc content were determined using inductively coupled plasma mass spectrometry, and iron was assessed using flame atomic absorption spectroscopy. The results were analyzed according to select clinical variables.

Results: Copper content was increased homogenously in all investigated structures of the WD brains compared to controls (41.0 ± 18.6 μg/g vs.5.4 ± 1.8 μg/g; P<0.01). The mean concentrations of iron, manganese, and zinc were similar in WD and controls, but the iron level in the nucleus dentatus was higher in WD compared to controls (56.8 ± 14.1 μg/g vs. 32.6 ± 6.0 μg/g; P<0.05). Gender, age, and type and duration of WD treatment did not impact brain metals storage, but some correlations between the duration of the disease and copper and iron accumulation were observed.

Conclusions: During the course of WD, copper accumulates equally in different parts of the brain. Zinc and manganese do not seem to be involved in WD pathology, but increased levels of iron were found in the nucleus dentatus. Thus, additional studies of brain iron accumulation in WD are needed.