Background: To investigate the usefulness of cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels as a candidate biomarker of neurodegeneration in Alzheimer's disease (AD), Parkinson's disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).Methods: We performed a systematic search of PubMed, the Cochrane Library, SCOPUS, and Google Scholar to find studies that investigated the CSF levels of NSE in AD, PD, DLB, and/or MSA. For each

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... se, we pooled all available data and performed a meta-analysis, and meta-regression analyses of age and sex were conducted when significant in the main analysis.Results: Twenty studies were included (13 for AD, 8 for PD/PDD/DLB, and 4 for MSA). Significantly elevated CSF NSE levels were detected in AD (Hedges' g = 0.822, 95% confidence interval [95%CI]: 0.332 to 1.311, p = 0.0010), but the data exhibited high heterogeneity (I2 = 88.43%, p<0.001). The meta-regression analysis of AD showed that age (p<0.001), but not sex, had a significant effect on NSE. A meta-analysis of all the pooled data for PD/PDD/DLB did not show any significant changes in the CSF NSE level, but a sub-group analysis of PDD/DLB revealed significantly elevated CSF NSE levels (Hedges' g = 0.507, 95%CI: 0.020 to 0.993, p = 0.0412). No significant changes in CSF NSE levels were detected in MSA.Conclusions: This study provided evidence about the usefulness of CSF NSE levels as a biomarker in AD and PDD/DLB, and age was found to affect the CSF NSE levels of AD patients.