Global Survey Reveals How Neurofilament Tests Are Used in Neurological Care

Neurofilament proteins — particularly neurofilament light chain (NfL) and neurofilament heavy chain (NfH) — are structural components of neuronal axons that are released into cerebrospinal fluid (CSF) and blood following axonal injury. Their quantification has emerged as one of the most promising pan-neurological damage biomarkers, with elevated levels observed across a broad spectrum of conditions including Alzheimer's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson's disease, traumatic brain injury, and prion diseases. Despite a rapidly growing body of research, the translation of neurofilament testing into standardized clinical practice has lagged behind scientific interest.

This study presents a comprehensive global overview of current clinical use and reporting practices for neurofilament quantification. The authors surveyed and compiled data from a large international consortium of laboratories and clinical centers spanning more than 20 countries across Europe, North America, South America, and Asia. The survey assessed which neurofilament subunits are measured (NfL vs. NfH), which biological matrices are used (CSF vs. serum/plasma), which assay platforms are employed (e.g., Simoa, Lumipulse, Ella, ELISA), how reference intervals are established, and how results are communicated to clinicians.

Key findings revealed substantial heterogeneity in practice. NfL in CSF was the most widely measured analyte, followed by serum NfL, reflecting the growing interest in blood-based testing due to its non-invasive nature. However, assay platforms varied considerably between centers, and reference intervals — critical for interpreting whether a patient's value is abnormal — were derived using different methodologies, age-stratification approaches, and control populations. Many laboratories reported using in-house reference ranges rather than internationally validated cutoffs, raising concerns about inter-laboratory comparability. Reporting formats also differed widely: some centers provided quantitative values with reference ranges, others issued qualitative interpretations, and few included age-adjusted percentile scores or disease-specific context.

The clinical indications for ordering neurofilament tests also varied by country and institution. MS monitoring (particularly for treatment response and disease activity), ALS diagnosis and progression tracking, and Alzheimer's disease workup were the most common indications. Prion disease and traumatic brain injury were less consistently covered. Notably, blood-based NfL testing was more common in research-oriented centers, while CSF NfL remained dominant in routine clinical laboratories, partly due to established workflows around lumbar puncture for other CSF biomarkers.

The authors emphasize that while neurofilament biomarkers hold enormous clinical promise, the current landscape of fragmented practices undermines their utility. They advocate for international harmonization efforts — including certified reference materials, commutability studies across platforms, consensus-based age-stratified reference intervals, and standardized reporting templates — as essential next steps. The paper also highlights the need for regulatory approval pathways in jurisdictions where neurofilament assays remain research-use-only, and calls for education initiatives targeting neurologists and laboratory physicians on appropriate test ordering and result interpretation.