Meta-analysis of cerebrospinal fluid neuron-specific enolase levels in Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy

Background: This study examined 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 measured CSF NSE levels in AD, PD, DLB, and/or MSA. For each disease, we pooled all available data and performed a meta-analysis, and meta-regression analyses of age and sex were conducted if the main analysis found a significant association. 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 (I-2 = 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 CSF NSE levels. A meta-analysis of 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: The CSF NSE level may be a useful biomarker of neurodegeneration in AD and PDD/DLB. Age was found to affect the CSF NSE levels of AD patients.