| Objective: Up to now,there are nearly 40 million people being attacked by dementia in the world.Most people with dementia are elder than 60 years old.Worst of all,this amount at least is expected to double every 20 years until 2050.The good news is that,we have prevented people from dementia for better vascular care.As the most prevalent cause of dementia,Alzheimer's disease(AD)is a fearful progressive neurodegenerative disease.In the beginning of AD,people just have the symptom of short-term memory failure and behavior deficiency.Subsequently,people will show progressive decreased ability of daily life and various mental disorders.Ultimately this irrepressible disease will lead to death.With the increase amount of people with AD,society has to bear a vast cost on this disease,so it has become the most careful healthy issue in the world.However,there are no competent therapeutic measures to halt or cure the progression of AD until now.Likewise,although many biomarkers for early diagnosis have been found,they looked like to be invalid and unacceptable.For that reason,clarifying the mechanism of AD is extremely vital to seek therapeutic measures which can delay or prevent this cureless disease.Previously,the features of AD pathology mainly include extracellular amyloid-?(A?)deposition,neurofibrillary tangles(NFTs)inside neurons,neurons loss,innate immune activation,mitochondrial dysfunction,oxidative stress and transition metal accumulation.With a better understanding of this disease,transition metal accumulation has been on focus.Some researchers have indicated that zinc was detected in the brain of AD patients in the form of zinc-A? complexes.Thus,zinc was suggested an important role in the pathogenesis of AD.Zinc ions can bind with A?,promote A? aggregation,and accentuate plaque formation.In addition,these metal ions can also interfere the progressing and function of amyloid precursor protein(APP).Moreover,they have also been suggested to taking a part in tau protein abnormalities by influencing the tau protein phosphorylation and inducing its aggregation.In addition,oxidative stress caused by the dyshomeostasis of these metal ions and interaction of pathological metal-protein may be another mechanism of neurodegeneration associated with AD.Taken into consideration the important effects of zinc in AD,we have designed a replication study in serum.Subsequently,we completed a meta-analysis of all published study from 1984 to 2017 about the topic of association between serum zinc and AD,and we also add the result of our replication study into the meta-analysis.Method: To assess the association between serum zinc and AD,we carried out a replication study of serum zinc levels in patients with AD.We selected 83 cases of sporadic patients with AD as a case group and 83 independent individuals as a healthy control group.All the subjects were northern Han Chinese.In order to reduce the influence of confounding factors on the results,we strictly matched the age and gender of the AD patients and healthy controls.All subjects were requested to fasting from last night.In the next morning,a 5 milliliter of venous blood sample was placed in serum tubes by intravenous puncture from all subjects.The samples were centrifuged at 3,000 rpm for 10 minutes at 4°C.Previous to analysis,the supernatant was placed in a polypropylene tube and stored in a-80°C freezer.We should perform experiment as soon as possible to avoid repeated thawing of serum samples.At first,we added the sample to the reagent and made them mixed thoroughly for half an hour.Then the parameters of the atomic absorption spectrometer were adjusted to the optimum state,and the calibration curve was made by the corresponding BH series atomic absorption spectrometer calibration solution(r ? 0.9950),and then the quality control sample of the BH series atomic absorption spectrometer was determined.When the results of the determination of the quality control sample are qualified,we start measure our experiment sample.Care should be taken when determining: The amount of sample to be added must be accurate.And we should mix quickly after adding the reagent to prevent condensation.Samples should be determined as soon as possible.If they are not detected immediately,they should be stored in a refrigerator(2-6°C)and can not be stored for more than two weeks.In addition,we performed a systematic search of all published studies from 1984 to 2017.Then we conducted a meta-analysis according to the results of this replication study and all included studies.In our meta-analysis,weighted mean difference(WMD)was used to eliminate the influence from the absolute values of AD and control groups.95% confidence intervals(CI)were used to assess the precision of results.Result: Our replication study suggested that the age(AD,73.99±7.13;healthy control,72.24±7.48;p=0.126)and sex distribution(?2=0.026 df(1)p = 0.872)between AD group and healthy control group did not show any difference.Be different from previous study,the result of replication study indicated that serum zinc maybe not associated with AD.Reviewing the experiment,we put the blame on our samples size.The small sample may lead to low statistical power.Our meta-analysis demonstrated that the zinc level in serum of patients with AD was significantly lower than healthy control group,but the heterogeneity(95.5%)was high.For the possibility of women percentage as a confounder factor,we conducted a regression analysis and the results showed that changes in serum zinc levels did correlate with sex ratios(p=0.041).In addition,we also respectively performed regression analysis for the measurement method(p=0.244),country(p=0.346),and mean age(p=0.077),as possible confounding factors.The results showed that there was no correlation between changes in serum zinc levels and these factors.Conclusion: In light of the results of replication study and meta-analysis,we can conclude that the zinc level in serum of patients with AD was significantly lower than healthy control group,and the variation of zinc level in patients with AD were associated with the percentage of women.From the above,zinc plays an important role in the pathogenesis of Alzheimer's disease. |
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