PT  - JOURNAL ARTICLE
AU  - Jasmini Alagaratnam
AU  - Sophia von Widekind
AU  - Davide De Francesco
AU  - Jonathan Underwood
AU  - Paul Edison
AU  - Alan Winston
AU  - Henrik Zetterberg
AU  - Sarah Fidler
TI  - Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis
AID  - 10.1136/bmjno-2021-000143
DP  - 2021 Jun 01
TA  - BMJ Neurology Open
PG  - e000143
VI  - 3
IP  - 1
4099  - http://neurologyopen.bmj.com/content/3/1/e000143.short
4100  - http://neurologyopen.bmj.com/content/3/1/e000143.full
SO  - BMJ Neurol Open2021 Jun 01; 3
AB  - Objective To assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein.Methods We searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included. We conducted a random-effects meta-analysis to calculate the overall pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the I2 statistic test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to blood NfL assay: single-molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) assay or ELISA.Results Data were extracted from 36 articles, including 3961 paired CSF and blood NfL samples. Overall, 26/36 studies measured blood NfL using Simoa, 8/36 ECL, 1/36 ELISA and 1 study reported all three assay results. The overall meta-analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72. Heterogeneity was significant: I2=83%, p<0.01. In sensitivity analyses, the pooled correlation coefficient was similar for studies measuring blood NfL using Simoa and ECL (r=0.69 and r=0.68, respectively) but weaker for ELISA (r=0.35).Conclusion Moderate correlations are demonstrated between CSF and blood NfL, especially when blood NfL was measured using Simoa and ECL. Given its high analytical sensitivity, Simoa is the preferred assay for measuring NfL, especially at low or physiological concentrations, and this meta-analysis supports its use as the current most advanced surrogate measure of CSF NfL.PROSPERO registration number CRD42019140469