| Background: Neurofilament light chain(NFL)was one neurofilament subunit,which was considered as a main structure of neurofilaments to maintain axonal stability and make axons grow.In neurodegenerative diseases,NFL is released into the interstitial fluid due to the disruption of the axonal membrane,and is eventually released into cerebrospinal fluid(CSF)and blood.High levels of CSF NFL have been reported frequently in patients with neurodegenerative diseases,such as Alzheimer disease(AD),amyotrophic lateral sclerosis(ALS),frontotemporal dementia(FTD),compared to controls.Although analysis did not show a significant result in Parkinson disease(PD)diagnosis,it has indicated that CSF NFL could be used in differential diagnosis for PD and PD-related disorders.Compared with CSF,the method for blood samples is noninvasive and convenient.Furthermore,a study has indicated that blood NFL levels are correlated with CSF NFL(correlation coefficients of 0.75 to 0.97).A comprehensive meta-analysis is warranted to assess NFL performance in the diagnosis and differential diagnosis among different types of neurodegenerative diseases.Methods: PubMed,Web of Science and Science Direct had been retrieved.All studies require statistical methods for case-control,retrospective or prospective cohorts.Articles were excluded if they met the following criteria: 1)the number of participants was less than 10,2)quantitative methods were not used to define the targets,3)the controls had other neurological,psychiatric or physical diseases which would confound the results,4)the measured target must be human being,5)studies only had a neurodegenerative disease cohort or a control cohort,or didn’t have comparison,6)treatment of these diseases was used.Information,including numbers of patients and controls,age of participants,female ratio and the concentration of NFL,was extracted from these articles.During data extraction,we only used baseline data if this was a longitudinal study,and the articles with longest follow-up were included if the research was with different follow-up.If some data were not eligible,we converted them to conform to our data requirement.To estimate the quality of articles,the quality assessment method which mixed three templates of quality assessment with 18questions(1-14 questions were from the Swedish Agency for Health Technology Assessment and Assessment of Social Services on the basis of Quality Assessment of Diagnostic Accuracy Studies tool(QUADAS),15-17 questions were from Standards for Reporting Diagnostic Accuracy(STARD),and question18 was from A Measurement Tool to Assess Systematic Reviews(AMSTAR))and three additional rows which included the definition of controls,autopsy diagnosis and final assessment of quality was used.The ratio of means method(RoM method)was used to evaluate the difference in NFL concentration between patients and controls.The 95% CI of ratio was calculated by the delta method mentioned in the introduction of RoM method.It’s believed that there is a significant difference if the P value was less than or equal to 0.05.Funnel plots were constructed to assess the publication bias.Random effects meta-analysis was used in Stata version 12.0 for these analyses.Results: A total of 36 eligible articles were finally included in this study.All ratios of AD patients versus controls were above one,and the average ratio is 2.01(95%CI: 1.70-2.38,P<0.0001).Ratios of comparisons between patients with FTD and controls were all above one and average ratio was 3.65(95%CI: 3.13-4.26,P<0.0001).The average ratio of Disease of Lewy bodies(DLB)was 1.76(95%CI: 1.57-1.98,P<0.0.001).The results of PD showed no significant difference in NFL level between PD patients and controls and the average ratio of PD was 1.11(95%CI: 0.96-1.29,P=0.142).All NFL ratios of progressive supranuclear palsy(PSP)patients versus controls were above one,and the average ratio was 2.71(95%CI: 2.20-3.34,P<0.0001).The average ratio of multiple system atrophy(MSA)was 4.19(95%CI: 3.25-5.39,P<0.0001).The average ratio of difference between ALS patients and controls was 7.68(95%CI: 2.81-21.04,P<0.0001).The average ratio of multiple sclerosis(MS)was 3.83(95%CI: 2.88-5.09,P<0.0001).NFL concentration differed significantly between Creutzfeldt-Jakob disease(CJD)patients and controls,and the average ratio was 9.96(95%CI: 5.98-16.59,P<0.0001).Average ratio between HD patients and controls was 6.20(95%CI: 5.25-7.33,P<0.0001).NFL is detectable in blood plasma or serum.The average ratio of AD was 1.68(95%CI: 1.38-2.04,P<0.0001).The ratio of FTD was 3.97(95%CI: 3.05-5.17).The ratio of MSA was 1.91(95%CI: 1.46-2.51).Average ratio of comparisons between ALS patients and controls was 3.26(95%CI: 2.63-4.03,P<0.0001).In the comparison of the NFL concentration between CJD patients and controls,the average ratio was 6.45(95%CI: 3.55-11.71).Funnel plots were used to assess the publication bias.Conclusions: NFL is a significant biomarker that distinguishes patients with neurodegenerative diseases from controls,whereas it shows no significant difference between PD patients and controls.However,except for the differential diagnosis between PD and PD-related disorders,NFL is not appropriate for differential diagnosis among other types of neurodegenerative diseases.Blood NFL levels were higher in patients with neurodegenerative diseases than controls,indicating NFL in blood is a potential biomarker for neurodegenerative diseases,which merits verification in more studies and larger cohorts.Our study indicated that NFL as a potential biomarker plays an important role in the early diagnosis and differential diagnosis of neurodegenerative diseases,and it is very valuable in relieving the global health problem of neurodegenerative diseases. |
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