Environmental, Genetic and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic and Neural Sciences, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy.
Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
Neuroepidemiology. 2020;54(1):1-23. doi: 10.1159/000502357. Epub 2019 Aug 27.
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 patients 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.
帕金森病（PD）是仅次于老年痴呆症的最常见神经退行性疾病。尽管 PD 的确切病因仍不清楚，但患 PD 的风险似乎与遗传和环境因素的综合作用有关。这也包括对营养和毒理学相关微量元素的异常暴露。
在这项系统评价和荟萃分析中，我们总结了病例对照研究的结果，这些研究比较了 PD 患者和对照组在血液（全血、血清/血浆）或脑脊液（CSF）中硒、铜、铁和锌水平。
我们进行了系统的 PubMed 搜索，选择了报告不同标本中患者和对照硒元素水平的研究。我们使用随机效应模型进行荟萃分析，计算血液或 CSF 中硒、铜、铁和锌水平的加权均数差（WMD）及其相应的 95%置信区间。
我们检索了 56 篇论文，报告了 CSF 中硒（病例/对照：588/721）、铜（2190/2522）、铁（2956/3469）和锌（1798/1913）含量的数据。与对照组相比，CSF 中的硒含量明显更高（+51.6%；WMD 5.49；95%CI 2.82 至 8.15），而血清中的硒含量相似（-0.2%；WMD -0.22；95%CI -8.05 至 7.62）。对于铜，CSF 中的铜含量略有升高，而血清中的铜含量略有降低（+4.5%；WMD 1.87；95%CI -3.59 至 7.33，和-4.5%；WMD -42.79；95%CI -134.35 至 48.76）。CSF 中的铁水平也略有升高（+9.5%；WMD 9.92；1.23 至 18.61），而血清/血浆中的铁水平降低（-5.7%；WMD -58.19；95%CI -106.49 至 -9.89）和全血中的铁水平降低（-10.8%；WMD -95.69；95%CI -157.73 至 -33.65）。相反，CSF 中的锌水平（-10.8%；WMD -7.34；95%CI -14.82 至 0.14）和血清/血浆中的锌水平（-7.5%；WMD -79.93；95%CI -143.80 至 -16.06）也较低。疾病持续时间较长可能与 CSF 或血液中微量元素水平整体较低有关。
由于研究结果和 CSF 与循环外周血相比的更大相关性，本荟萃分析表明，中枢神经系统中硒以及可能的铜和铁的过度暴露可能是疾病的危险因素，而锌可能具有保护作用。
