BACKGROUND:
Dementia is a common symptom in Parkinson’s disease (PD), occurring in up to 80% of PD patients within 20 years following initial diagnosis, resulting in a condition known as Parkinson’s disease dementia (PDD). It is currently unknown why some individuals with PD go on to develop PDD while others remain free of cognitive decline until death. One possible contributor is metallomic dysfunction, with previous studies showing metallic alterations across the PDD brain—most notably, widespread Cu decreases. In this study, we set out to ascertain whether similar alterations were also present in the PD brain.
METHODS:
Levels of the essential metals Na, Mg, K, Ca, Mn, Fe, Cu, and Zn and the metalloid Se were determined in tissues from seven brain regions obtained from nine confirmed PD cases and 15 matched controls using inductively coupled plasma mass spectrometry (ICP-MS). Multiple linear regression was used to determine potential confounder effects from variables such as age, post-mortem delay, and α-synuclein Braak stage. Results were compared with findings previously obtained in PDD brains using the same methods.
RESULTS:
Only one significant case-control difference was found in the PD brain: decreased Cu in the medulla oblongata. This contrasts markedly with the widespread metallic dysfunction observed in the PDD brain. PD and PDD cases were well-separated by PCA analysis. In the PD cohort, tau Braak stage correlated with Cu levels in several brain regions; however, these correlations were not retained when PDD cases were included in the analysis.
CONCLUSION:
In contrast to PDD cases, PD cases show a striking lack of metallic changes in the brain. This data suggests that a resistance to metallomic dysfunction may contribute to resilience against cognitive impairment in those who do not go on to develop dementia in PD.