Neurofilament Light Chain

Neurofilaments are the primary structural components of the neuronal cytoskeleton, providing mechanical stability to axons and regulating their caliber. They consist of three subunits: light (NfL), medium (NfM), and heavy (NfH) chains. NfL is the most abundant subunit and, critically, the one that is most reliably detected in blood using current ultra-sensitive immunoassay platforms such as single-molecule array (Simoa) technology. When axonal injury occurs — regardless of cause — neurofilaments are released into the surrounding extracellular space, enter the cerebrospinal fluid, and ultimately reach the bloodstream.

What distinguishes NfL from many other biomarkers is its broad sensitivity to neuroaxonal damage across disease categories. Elevated blood NfL levels have been documented in multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, traumatic brain injury, HIV-associated neurocognitive disorders, and peripheral neuropathies. This cross-disease sensitivity makes NfL a powerful general indicator of neurological activity, though it requires clinical context to interpret which specific pathology is responsible for an elevation.

Blood NfL concentrations increase naturally with age, reflecting the gradual loss of neurons that accompanies normal aging. Reference ranges must therefore be age-adjusted. Despite this, NfL levels that exceed age-expected norms are associated with active neurological disease and may precede clinical symptom onset in some conditions, making NfL a candidate biomarker for preclinical disease detection and treatment monitoring.

Prevena Health is exploring whether continuous NfL monitoring may support earlier detection of neuroaxonal injury and more granular tracking of neurological disease activity. Current NfL measurement relies on periodic venous blood draws, which capture a single point on what may be a dynamically evolving trajectory. Continuous surveillance through a wearable biosensor aims to fill the gaps between clinical visits, potentially capturing transient NfL elevations that point-in-time sampling might miss.

This approach may be particularly relevant for populations undergoing disease-modifying therapy for multiple sclerosis or participating in clinical trials for neurodegenerative diseases, where frequent NfL measurements could provide richer pharmacodynamic data. Prevena is also investigating the potential of continuous NfL monitoring in sports medicine and military settings, where repeated head impacts may cause cumulative axonal damage that individual assessments fail to capture.