It is currently unknown why some individuals with Parkinson's disease (PD) go on to develop dementia [Parkinson's disease dementia (PDD)], whereas others do not. One possibility is differences in susceptibility to metallomic dysregulation. A previous study of the PDD brain identified substantive perturbations in metal levels, including severe multiregional decreases in Cu. The current work uses the same methods to ascertain whether this metallomic dysfunction is also present in the PD brain. To do this, tissue from 9 PD cases free of cognitive decline and 15 equivalent controls was obtained from 7 brain regions. Levels of Na, Mg, K, Ca, Mn, Fe, Cu, Zn, and Se were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Multiple linear regression analysis was used to determine any potential confounder effects. Results were compared with those previously obtained for PDD. It was found that decreased Cu in the medulla was the only statistically significant case-control difference observed in the PD brain; this contrasts markedly with the widespread metallic dysfunction observed in PDD. PD and PDD cases were well separated by PCA analysis. In the PD cohort, tau Braak stage correlated with Cu concentrations in several regions, but these correlations were not retained when including PDD cases. There is a marked difference in the metallomic profiles of PD and PDD, with an almost complete lack of metallic involvement observed in the former. This resistance to metallomic dysfunction may contribute to resilience against cognitive impairment in individuals with PD who do not develop dementia.
© The Author(s) 2025. Published by Oxford University Press.