# Perturbations in levels of essential metals less severe in Parkinson’s disease without dementia than in Parkinson’s disease dementia

## TL;DR

The study finds that Parkinson’s disease without dementia shows much less disruption in brain metal levels compared to Parkinson’s disease with dementia.

## Contribution

The study reveals that metallomic dysfunction is significantly less severe in PD without dementia than in PD dementia.

## Key findings

- Decreased Cu in the medulla was the only significant metal change in PD without dementia.
- PD and PDD cases were clearly separated by PCA analysis based on metallomic profiles.
- Metallic dysfunction is almost absent in PD without dementia, suggesting a protective factor against cognitive decline.

## Abstract

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.

Graphical AbstractThe PD brain shows much lower overall metallomic involvement than the PDD brain, with decreased Cu in the medulla oblongata being the only metallic alteration observed across seven investigated brain regions.

The PD brain shows much lower overall metallomic involvement than the PDD brain, with decreased Cu in the medulla oblongata being the only metallic alteration observed across seven investigated brain regions.