Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD

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... ients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.