| Background:Alzheimer's disease(AD)is a progressive degenerative disease of the central nervous system.Pathological changes mainly included senile plaques formed by ?–Amyloid(A?)aggregation,high phosphorylated tau protein aggregation,neurofibrillary tangles(NFTs)and neuronal damage.Various hypotheses are available to explain the etiology and pathogenesis of AD,such as abnormal protein deposition,oxidative stress,mitochondrial dysfunction,transition metal accumulation and inflammation.High concentration of metal ion was observed in senile plaque of AD patients.Meanwhile,more and more studies focus on the hypothesis of excessive metal pathogenicity.Copper is a necessary trace element to maintain normal physiological function of human body,and its metabolic disorder can lead to multi-system disease.Serum copper mainly consists of copper bound with ceruloplasmin and copper with non-ceruloplasmin,also known as free copper.Studies have found that transition metal copper can bind to ?-amyloid protein(A?).On the one hand,metal copper can accelerate A? deposition and the formation of senile plaques.On the other hand,it may induce oxidative stress,finally leading to neurodegeneration.In addition,new studies have shown that copper not only interferes with the processing and function of ?-amyloid precursor protein(A?pp),relates to the expression and secretion of apolipoprotein E(apolipoprotein Apo E),but also participates in the hyperphosphorylation of tau and the aggregation of neuronal fibrillary tangles.More and more people are studying the relationship between metal copper and the risk of Alzheimer's disease(AD),but the results are somewhat ambiguous.Objective : Considering the importance of transition metal copper in AD,some researchers have further studied to see whether the changes in copper content in serum can be used as diagnostic criteria for AD by measuring serum copper levels.Making a comprehensive meta-analysis of the completed researches combined with our case-control study is to explore the correlation between serum copper content and AD,provide a new idea for the occurrence and development of AD and also provide a new basis for its prevention and diagnosis.Methods: A case-control study was conducted to collect 83 cases of sporadic AD as case group and 83 healthy controls(age and sex matched)among Han Chinese population in northern China.We took the peripheral venous blood of all the subjects.Using centrifuge obtained the corresponding liquid supernatant.The content of copper in serum was determined by flame atomic absorption spectrometry(FAAS,Bo Hui 5300 S,Beijing,China).According to demographics and cognitive characteristics,we describe AD patients and healthy controls.We collected and collated the necessary data,including age,sex ratio,total average and standard deviation of serum copper in the case group and control group.The data were analyzed with SPSS19.0 software to obtain a p-value,chi-square value or t value.At the same time,we made a compare with the t-test of independent sample and the chi-square test of sex distribution.In all statistical analyses,a p-value of less than 0.05 was considered significant.Because of the difference of race and the number of samples included,the accuracy of the conclusion will be affected.We have systematically searched and screened literatures published after 1984 in the databases of PUBMED,MEDLINE,EMBASE,the Cochrane library and BIOSIS previews.A total of 40 related articles were found,the types of studies included were case-control studies,and 26 related articles were identified according to the inclusion and exclusion criteria.A total of 1768 AD cases and 2541 healthy controls were enrolled.Combined with this case-control study,STATA and R software were used to integrate and analyze the available data for each study,and the corresponding forest maps were obtained.Taking into account the heterogeneity effect,through sensitive analysis,the data were analyzed again using the same method,after excluding trials that had a significant impact on the results.We can use funnel graphs to evaluate publication bias.Subsequently,meta-regression was performed on possible confounding factors,such as assessment methods,average age,percentage of women and country.The correlation between serum copper level and AD was described and discussed by synthesizing the results of meta-analysis.Results:A case-control study data showed that in Chinese northern Han population,Serum copper levels distinctly increase(t = 5.832,P < 0.05).Additional,age(AD group,mean age 73.99 years,standard deviation 7.13;control group,average age 72.24 years,standard deviation of 7.48;p=0.126)and gender(x2 = 0.026,DF(1)P = 0.872)had no statistical differences in serum copper level in case and control groups.Data from this experiment associating with data from literature published after 1984 according to inclusion and exclusion criteria showed that the serum copper level in case compared with healthy control group significantly increased(WMD= 10.474,P < 0.001),and highly heterogeneous to 99%.Consider high heterogeneity,we ran a sensitivity analysis,after excluding the study of Singh et al,and found that serum copper in AD are significantly higher(WMD = 9.618;P<,0.01),followed by heterogeneity as 94.2.0%.It can be seen that the heterogeneity was obviously reduced,but still high.Subsequently,we performed a meta-regression analysis about some possible confounding factors,such as evaluation methods(P = 0.607),mean age(P = 0.861),the percentage of women(P = 0.940)and national(P = 0.0094 the results showed that copper).There was no significant correlation between the changes in the copper level and these factors.The results of our case-control study were in agreement with the results of meta-analysis.Conclusions:A case-control study found that there was a significant difference in serum copper levels between AD patients and healthy controls in the Han population of northern China.A meta-analysis was conducted in combination with published relevant studies in the serum of AD patients.The level of copper is significantly increased,which can be used as a serum biomarker in AD patients and participate in the pathogenesis of AD,which is of significance for the diagnosis of AD patients. |
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