CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression

Abstract

Objectives: This study compared neurofilament light chain (NFL) levels in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with levels in patients with other neurological diseases and healthy controls and assessed correlations between NFL levels and clinical indicators of sALS. Methods: We used enzyme-linked immunosorbent assays to determine the NFL levels in the CSF of 45 patients with sALS, 21 patients with other central nervous system diseases (OCNSDs), 18 with immune-mediated peripheral neuropathy (IMPN), 14 with non-immune-mediated peripheral neuropathy (NIMPN), and 19 healthy controls (HCs). Results: The median NFL levels in the CSF of the sALS, OCNSD, IMPN, NIMPN, and HC groups were 6510, 5372, 4320, 1477, and 756 pg/mL, respectively. The CSF NFL levels did not differ significantly among the sALS, IMPN, and OCNSD groups, but were significantly higher than those of the NIMPN and HC groups. The NFL CSF levels were significantly higher in the NIMPN group than the HCs. There was a negative correlation between the NFL level and ALS function score (ALSFRS-R), and a positive correlation with the disease progression rate in patients with sALS. Conclusion: CSF NFL may not be sufficient to distinguish ALS from other central nervous system diseases or peripheral neuropathy, but it predicts ALS severity and progression.

Cerebrospinal Fluid Neurofilament Light Chain (NfL) Predicts Disease Aggressiveness in Amyotrophic Lateral Sclerosis: An Application of the D50 Disease Progression Model

“…Besides disease aggressiveness, three covariates exhibited statistically significant effects on CSF NfL levels of ALS patients. In accordance with previous studies, age showed a positive association with CSF NfL ( Vågberg et al, 2015 ; Gong et al, 2018 ; Steinacker et al, 2018b ; Sun et al, 2020 ). This most likely reflects the degenerative process in the brain associated with normal aging, which leads to a slowly progressive rise of neurofilaments in the CSF.…”

Blood Neurofilament Light Chain in Parkinson’s Disease: Comparability between Parkinson’s Progression Markers Initiative (PPMI) and Asian Cohorts

“…In recent decades, several biomarkers in the body fluid, such as orexin, 8-Hydroxy-2′-Deoxyguanosine, peripheral proteasomes, caspases, dopamine, dopamine receptor, alpha-synuclein, and apolipoprotein A1 (ApoA1), have been suggested to be diagnostic of PD [ 11 ]; however, some of these biomarkers fail to reflect the disease course while others only exhibit vague results. Recently, significant aberration in neurofilament light chain (NfL) levels have been associated with Alzheimer’s disease (AD) [ 12 ], amyotrophic lateral sclerosis [ 13 ], multiple sclerosis [ 14 ] and cerebral vascular disease [ 15 ]. NfL, a 68 kDa neuronal cytoplasmic protein, is considered critical for radial growth and axon stability, and the release of NfL into blood and/or cerebrospinal fluid (CSF) circulation reflects axonal damage [ 16 , 17 ].…”

Biomarker discovery and development for frontotemporal dementia and amyotrophic lateral sclerosis

“… 73 Elevated CSF NfL is indicative of amyotrophic lateral sclerosis severity and progression. 74 Amongst neurodegenerative diseases, frontotemporal dementia and amyotrophic lateral sclerosis exhibit the greatest elevations in CSF NfL. 75 Compared to healthy controls, NfL levels are ∼20-fold higher in amyotrophic lateral sclerosis CSF, whereas they are 3-fold higher in frontotemporal dementia CSF.…”