Cerebrospinal Fluid α-synuclein And Tau As Biomarkers For Dementia With Lewy Bodies:Meta-analysis

Objective:Dementia with Lewy bodies（DLB）is a neurodegenerative disease for which there are currently no reliable biomarkers to guide clinical diagnosis and to help determine prognosis.The main component of Lewy bodies is α-synuclein,which has long been considered a neuropathological feature of Parkinson’s disease（PD）;and tau protein in cerebrospinal fluid（CSF）is regarded as a marker for the diagnosis of Alzheimer’s disease（AD）.Whereas,there is co-pathology of α-synuclein and tau protein in the CSF of DLB.Several scholars have observed that α-synuclein and tau can promote mutual aggregation in animal models and dementia patients;thereby,aggravating neurodegeneration and worsening their prognosis.There is still some controversy regarding the specific levels of α-synuclein and tau in the CSF of DLB patients.Therefore,we included a large number of studies for meta-analysis to investigate whether α-synuclein and tau in CSF can be used as biomarkers to provide some help for the clinical diagnosis of DLB.Therefore,we conducted a meta-analysis and included a large number of high-quality studies to assess the levels of α-synuclein and tau in the CSF of patients with DLB to explain the current differences and provide an more acceptable basis for the diagnosis of DLB.Methods:We retrieved studies with “Dementia with Lewy bodies”,“α-synuclein”,“cerebrospinal fluid”,and “tau” as keywords.We searched China National Knowledge Network（CNKI）,Wanfang Data Knowledge Service Platform,Pub Med,Embase and Web of Science from January 1,2000,to December 31,2021.Review Manager 5.4 and Stata 16 were used for meta-analysis.Subgroup,sensitivity,and meta-regression analyses were performed to identify sources of heterogeneity and strengthen the results.Result:Thirty-four studies were included in the meta-analysis of CSF tau levels in the DLB and control groups,with the total of 1,004 and 1,532 patients,respectively.Compared to the control group,DLB patients showed significantly higher CSF levels of tau（Weighted mean difference [WMD] = 76.70 [55.92,97.49],Z = 7.23,P <0.00001）.For the comparison of the levels of α-synuclein in the CSF of DLB patients and the control group,we found high heterogeneity among the 14 studies with a total of 492 and 575 patients.The random-effects model showed that the levels in the DLB group were significantly lower than those in the control group（WMD-95.25;[-162.02,-28.48];Z = 2.80;P = 0.005）.Mini-Mental State Examination（MMSE）score,Male ratio,and disease duration were not sources of heterogeneity on subgroup and meta-regression analyses.Sensitivity analysis revealed no significant differences.Conclusion:Higher levels of tau and lower levels of α-synuclein were in the CSF of patients with DLB than in the control group.Therefore,CSF tau and α-synuclein levels may be diagnostic biomarkers for DLB.