pNfH

pNfH, short for phosphorylated neurofilament heavy chain, is a post-translationally modified form of the neurofilament heavy chain (NF-H), a key structural component of myelinated axons. Neurofilaments regulate axonal caliber and conduction, and NF-H undergoes extensive phosphorylation during normal maturation. Following axonal injury or neurodegenerative processes, pNfH is released into the extracellular space and can be detected in cerebrospinal fluid (CSF) and blood, where its levels reflect axonal damage.

Measurement and interpretation: pNfH is measured with immunoassays using antibodies that recognize the phosphorylated epitope. Assays include ELISA and highly sensitive platforms such as single molecule array (SIMOA). Specimens commonly used are CSF and blood (serum or plasma). Because levels can vary with age, sex, and comorbidities, serial measurements and clinical context are important for interpretation.

Clinical relevance: In research and clinical settings, pNfH is used as a biomarker of axonal injury and disease activity. Elevated levels have been described in amyotrophic lateral sclerosis (ALS), spinal cord injury, traumatic brain injury, stroke, and some inflammatory or neurodegenerative conditions. In ALS and other diseases, pNfH concentrations often correlate with disease severity, progression, or response to therapy in trials, though not disease-specific.

Limitations and context: pNfH is a marker of neuroaxonal damage rather than a diagnostic test for a particular disorder. Levels may be influenced by blood-brain barrier integrity and peripheral clearance, and assay standardization varies between laboratories. Interpretation is enhanced when combined with other biomarkers, such as neurofilament light chain (NfL), and clinical information. See also neurofilament light chain.