Correlation between cerebrospinal fluid and blood neurofilament light protein: A systematic review and meta‐analysis

Abstract

AbstractBackgroundCerebrospinal fluid (CSF) neurofilament light protein (NfL) is a sensitive biomarker of central nervous system neuro‐axonal injury. A novel assay measuring blood NfL has been developed, avoiding the need for CSF sampling. Several studies have published correlations between CSF and blood NfL, but the pooled correlation is unknown. This meta‐analysis aims to determine the pooled correlation coefficient estimate between CSF and blood NfL, and to stratify by correlation technique and blood NfL assay.MethodWe searched Medline, Embase and Web of Science for published manuscripts in English, from their inception to July 9, 2019, according to PRISMA guidelines. We included studies reporting the correlation between CSF and blood (plasma/serum) NfL. We then conducted a random‐effects meta‐analysis to calculate the pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the Cochran Q test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to whether Spearman’s rank or Pearson’s correlation coefficient was reported (where unspecified, Pearson’s correlation was imputed), and according to blood NfL assay: single‐molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) or enzyme‐linked immunosorbent assay (ELISA).ResultData were extracted from 37 articles, including 3797 individuals. 23 studies reported Spearman’s rank and 10 studies reported Pearson’s correlation coefficient; correlation technique was unspecified in 4 studies. 29 studies used Simoa, 7 ECL and 1 ELISA. Results from the overall meta‐analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72, 95% confidence interval 0.56‐0.83, p<0.001 (Figure 1). Heterogeneity was significant: Q=206.2, p<0.0001. In sensitivity analyses, for studies quoting Spearman’s rank, the pooled estimate was r=0.66, p<0.001, while the pooled estimate was r=0.76, p<0.001 for studies quoting Pearson’s correlation. When stratified by blood NfL assay, the pooled correlation coefficient was similar for Simoa and ECL (r=0.70, p<0.001 and r=0.73, p<0.001, respectively), but weaker for ELISA (r=0.35, p=0.272).ConclusionStrong correlations are demonstrated between CSF and blood NfL, especially with Simoa and ECL blood NfL assays. Simoa is the preferred blood NfL assay due to its low detection limit, and this meta‐analysis supports blood NfL measured using Simoa, as a surrogate measure of CSF NfL.