scholarly journals Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity

2020 ◽  
Vol 94 (7) ◽  
pp. 2517-2522 ◽  
Author(s):  
Cristina Meregalli ◽  
Giulia Fumagalli ◽  
Paola Alberti ◽  
Annalisa Canta ◽  
Alessia Chiorazzi ◽  
...  
2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774309 ◽  
Author(s):  
Mariotto S ◽  
Farinazzo A ◽  
Monaco S ◽  
Gajofatto A ◽  
Zanusso G ◽  
...  

Background Neurofilament light chain (NF-L) levels reflect axonal damage in different conditions, including demyelinating disorders. Objectives We aimed to compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab), myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with neuromyelitis optica spectrum disorders and related disorders. Methods We analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive electrochemiluminescence immunoassay. Results Median NF-L levels were increased in 25 AQP4-Ab-positive patients (59 pg/ml) as compared with 22 MOG-Ab-positive cases (25 pg/ml), 52 seronegative patients (18 pg/ml), 25 multiple sclerosis patients (12 pg/ml) and 14 healthy controls (12 pg/ml). Conclusions Increased serum levels of NF-L in patients with AQP4-Ab or MOG-Ab might reflect an ongoing axonal damage and a more malignant disease course.


2019 ◽  
Vol 6 (6) ◽  
pp. 1134-1137 ◽  
Author(s):  
Marc Pawlitzki ◽  
Michaela Butryn ◽  
Florian Kirchner ◽  
Jacqueline Färber ◽  
Oliver Beuing ◽  
...  

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.


2019 ◽  
Vol 90 (8) ◽  
pp. 870-881 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Kaj Blennow ◽  
Paolo Calabresi ◽  
Massimiliano Di Filippo ◽  
Lucilla Parnetti ◽  
...  

In the management of neurological diseases, the identification and quantification of axonal damage could allow for the improvement of diagnostic accuracy and prognostic assessment. Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. Its levels increase in cerebrospinal fluid (CSF) and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including inflammatory, neurodegenerative, traumatic and cerebrovascular diseases. New immunoassays able to detect biomarkers at ultralow levels have allowed for the measurement of NfL in blood, thus making it possible to easily and repeatedly measure NfL for monitoring diseases’ courses. Evidence that both CSF and blood NfL may serve as diagnostic, prognostic and monitoring biomarkers in neurological diseases is progressively increasing, and NfL is one of the most promising biomarkers to be used in clinical and research setting in the next future. Here we review the most important results on CSF and blood NfL and we discuss its potential applications and future directions.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Quan-Fu Li ◽  
Yi Dong ◽  
Lu Yang ◽  
Juan-Juan Xie ◽  
Yin Ma ◽  
...  

Abstract Background Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. Methods Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. Results Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = − 0.4217, p = 0.0003) and brainstem volumes (r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat. Conclusions Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.


2021 ◽  
pp. 10.1212/CPJ.0000000000001116
Author(s):  
Efthalia Angelopoulou ◽  
Anastasia Bougea ◽  
Andreas Papadopoulos ◽  
Nikolaos Papagiannakis ◽  
Athina-Maria Simitsi ◽  
...  

Abstract:Purposeof review: To evaluate whether CSF and circulating neurofilament light chain (NFL), a marker of axonal damage, could discriminate Parkinson’s disease (PD) from atypical parkinsonian syndromes (APS).Recent findings:MEDLINE and SCOPUS were systematically searched, and fifteen studies were included (1035 PD patients,930 APS patients). CSF and circulating NFL levels were 1.26 and 1.53 standard deviations higher in APS compared to PD patients respectively [g=1.26 (95% CI 0.99-1.53);12 studies, 880 PD patients, 847 APS patients, g=1.53 (1.15-1.91);4 studies, 307 PD patients, 197 APS patients. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NFL, corresponding to average sensitivities of 86% (79-90%) and 91% (86-95%), and specificity of 88% (82-92%) and 76% (62-85%), respectively.Summary:These results strongly support the high diagnostic accuracy of both CSF and circulating NFL in differentiating PD from APS, highlighting their usefulness as promising biomarkers.


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