The multifaceted role of neurofilament light chain protein in non-primary neurological diseases

Abstract

The advancing validation and exploitation of cerebrospinal fluid and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarise the current evidence, future perspectives, but also limitations, of neurofilament light chain protein as a cerebrospinal fluid and blood biomarker in several medical fields, including intensive care, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurologic impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease 19 (COVID-19) pandemic and in normal aging. Altogether, current data outline a multifaceted applicability of cerebrospinal fluid and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.

Evidence of polygenic regulation of the physiological presence of neurofilament light chain in human serum

“…And, third, the nature of the study design of the sample populations included in the present study derived in an enrichment of individuals with depression, cardiovascular risk factors and cardiovascular disease. While most prior research focused on neurological conditions, recent studies have shown increased levels of sNfL in patients with cardiovascular or metabolic conditions and multimorbidity ( 39 ). In fact, we also showed this to be the case in the BiDirect study.…”

Serum neurofilament light chain in myasthenia gravis subgroups: An exploratory cohort and case–Control study

“…Due to the potential influence on sNfl levels, patients with a previous history of cancer were excluded, excepting thymoma ( 31 ). Other exclusion criteria were diagnosis of polyneuropathy, neurodegenerative diseases (atypical and typical parkinsonian disorders, frontotemporal dementia, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS)), central nervous inflammatory diseases (multiple sclerosis and autoimmune encephalitis), traumatic brain injury, and previous stay on intensive care unit (< 3 months) ( 32 ). Overall, 134 patients could be included for baseline analysis and were followed up to 3 years.…”

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome

“…Neurofilament light chain (NfL) is a protein that is found throughout the central and peripheral nervous system in the axons of nerve cells under physiological conditions, and in the blood and CSF in some pathologies involving significant nerve damages [ 36 ]. NfLs are the most abundant and soluble cytosolic subunits of the neurofilaments that give structural stability to the axons, dendrites, and somas [ 37 ].…”