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Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis

Alagaratnam, Jasmini, von Widekind, Sophia, De Francesco, Davide, Underwood, Jonathan, Edison, Paul, Winston, Alan, Zetterberg, Henrik and Fidler, Sarah 2021. Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis. BMJ Open Neurology 3 , e000143. 10.1136/bmjno-2021-000143

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license
Publisher: BMJ Publishing Group
ISSN: 2632-6140
Date of First Compliant Deposit: 2 September 2021
Date of Acceptance: 12 May 2021
Last Modified: 03 Sep 2021 13:30
URI: https://orca.cardiff.ac.uk/id/eprint/143820

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