Meta‐Analysis of Copper and Iron in Parkinson's Disease Brain and Biofluids

Abstract Background Variations in study quality and design complicate interpretation of the clinical significance of consistently reported changes in copper and iron levels in human Parkinson's disease brain and biofluids. Methods We systematically searched literature databases for quantitative reports of biometal levels in the degenerating substantia nigra (SN), CSF, serum, and plasma in Parkinson's disease compared with healthy age‐matched controls and assessed the quality of these publications. The primary outcomes of our analysis confirmed SN copper and iron levels are decreased and increased, respectively, in the Parkinson's disease brain. We applied a novel Quality Assessment Scale for Human Tissue to categorize the quality of individual studies and investigated the effects of study quality on our outcomes. We undertook a random‐effects meta‐analysis and meta‐regression subgroup analysis. Results In the 18 eligible studies identified (211 Parkinson's disease, 215 control cases), SN copper levels were significantly lower ( d, ‐2.00; 95% CI, ‐2.81 to ‐1.19; P < 0.001), and iron levels were significantly higher (d , 1.31; 95% CI, 0.38–2.24; P < 0.01) in Parkinson's disease. No changes were detected in CSF, serum, or plasma for any metals (29 studies; 2443 Parkinson's disease and 2183 control cases) except serum iron, which was lower in Parkinson's disease (14 studies; 1177 Parkinson's disease and 1447 control cases). Conclusions Reductions in copper levels and elevations in iron were confirmed as characteristic of the degenerating SN of Parkinson's disease. Iron in serum was also changed, but in the opposite direction to that in the SN and to a lesser extent. © 2019 International Parkinson and Movement Disorder Society