Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges.

Area of Science:

• Biomarker Discovery
• Neuroscience
• Clinical Diagnostics

Background:

• Neurofilament-light chain (Nf-L) is an early biomarker for axonal damage in neurodegenerative diseases (NDD) and traumatic brain injuries (TBI).
• Nf-L is now quantifiable in blood using ultrasensitive assays, expanding its clinical potential beyond cerebrospinal fluid (CSF).

Purpose of the Study:

• To review current Nf-L quantification methods in biofluids for clinical implementation.
• To address challenges in developing reference measurement procedures (RMP) and defining the measurand for Nf-L standardization.
• To discuss the impact of pathophysiological factors and clinical cut-offs for Nf-L.

Main Methods:

• Review of current immunoassays and ultrasensitive assays for Nf-L quantification.
• Discussion of mass spectrometry's role in developing RMP and defining the Nf-L measurand.
• Analysis of factors influencing Nf-L levels and clinical threshold establishment.

Main Results:

• Ultrasensitive assays enable Nf-L measurement in blood, offering broader clinical utility.
• Standardization requires reliable RMP, certified reference materials (CRM), and precise measurand definition due to Nf-L complexity.
• Mass spectrometry is a key tool for RMP development and measurand definition.

Conclusions:

• Standardization of Nf-L assays is critical for reliable clinical implementation in NDD and TBI diagnostics.
• Further development of RMP and clear measurand definitions are necessary for widespread Nf-L assay adoption.
• Understanding pathophysiological influences is essential for establishing accurate clinical cut-offs.