Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology

Abstract

Identifying neuroaxonal damage and quantifying the intensity of this process is a critical step in patient care because it may support diagnosis and help estimate the prognosis of neurological conditions. In addition, it is essential for the evaluation of drug candidates with disease-modifying potential. Neurofilament light protein (NfL) is an abundant cytoskeletal protein exclusively expressed by central and peripheral neurons. Elevated levels of NfL in cerebrospinal fluid (CSF) were first reported in neurodegenerative conditions more than 20 years ago,¹ sparking interest in the potential of this neuron-specific protein as a biomarker. Since then, elevated levels of NfL in CSF (cNfL) have been described in a number of neurological and psychiatric conditions. The magnitude of the increase in inflammatory, degenerative, infectious, ischemic, and traumatic neurological conditions, as well as in psychiatric disorders, varies between conditions and studies. To date, cNfL levels have not been compared systematically between neurological disorders, and patient numbers in individual studies are often low. A positive association between cNfL and age has been reported in healthy controls (HC)² but was not systematically investigated in neurological conditions and may alter the performance of this biomarker across age categories. Together, these questions limit clinical implementation of cNfL. To compare cNfL levels between diagnoses, assess the association of age and sex with these variables, and evaluate the potential of cNfL level as a diagnostic biomarker, we performed a systematic review and meta-analysis on individual data collected from studies reporting cNfL levels in diseases and controls.