scholarly journals Neurofilament light chain as a biomarker in neurological disorders

2019 ◽  
Vol 90 (8) ◽  
pp. 870-881 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Kaj Blennow ◽  
Paolo Calabresi ◽  
Massimiliano Di Filippo ◽  
Lucilla Parnetti ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Cerebrovascular Diseases ◽  
Axonal Damage ◽  
Neurofilament Light Chain ◽  
Future Directions ◽  
Neurofilament Light ◽  
Prognostic Assessment ◽  
Potential Applications

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.

scholarly journals Serum Neurofilament Light Chain in NMOSD and Related Disorders: Comparison According to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies Status

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774309 ◽  
Author(s):  
Mariotto S ◽  
Farinazzo A ◽  
Monaco S ◽  
Gajofatto A ◽  
Zanusso G ◽  
...  
Keyword(s):  
Light Chain ◽  
Malignant Disease ◽  
Serum Levels ◽  
Axonal Damage ◽  
Aquaporin 4 ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Spectrum Disorders ◽  
Multiple Sclerosis Patients ◽  
Demyelinating Disorders

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.

scholarly journals CSF Neurofilament light chain level predicts axonal damage in cerebral vasculitis

2019 ◽  
Vol 6 (6) ◽  
pp. 1134-1137 ◽  
Author(s):  
Marc Pawlitzki ◽  
Michaela Butryn ◽  
Florian Kirchner ◽  
Jacqueline Färber ◽  
Oliver Beuing ◽  
...  
Keyword(s):  
Light Chain ◽  
Cerebral Vasculitis ◽  
Axonal Damage ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Chain Level

scholarly journals Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

2021 ◽  
pp. 1-7
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

scholarly journals Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal

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.

scholarly journals Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75091 ◽  
Author(s):  
Johanna Gaiottino ◽  
Niklas Norgren ◽  
Ruth Dobson ◽  
Joanne Topping ◽  
Ahuva Nissim ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Diseases ◽  
Blood Levels ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa

2016 ◽  
Vol 54 (10) ◽  
Author(s):  
Jens Kuhle ◽  
Christian Barro ◽  
Ulf Andreasson ◽  
Tobias Derfuss ◽  
Raija Lindberg ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Neurological Diseases ◽  
Cytoskeletal Proteins ◽  
Response To Treatment ◽  
Analytical Sensitivity ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

AbstractBackground:Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are specific cytoskeletal proteins of neurons and their quantification has shown encouraging results as a biomarker for axonal injury.Methods:We aimed at comparing a widely used conventional ELISA for Nf light chain (NfL) with an electrochemiluminescence-based method (ECL assay) and a newly developed single-molecule array (Simoa) method in clinically relevant cerebrospinal fluid (CSF) and serum samples.Results:Analytical sensitivity was 0.62 pg/mL for Simoa, 15.6 pg/mL for the ECL assay, and 78.0 pg/mL for the ELISA. Correlations between paired CSF and serum samples were strongest for Simoa (r=0.88, p<0.001) and the ECL assay (r=0.78, p<0.001) and weaker for ELISA measurements (r=0.38, p=0.030). CSF NfL measurements between the platforms were highly correlated (r=1.0, p<0.001). Serum NfL levels were highly related between ECL assay and Simoa (r=0.86, p<0.001), and this was less visible between ELISA-ECL assay (r=0.41, p=0.018) and ELISA-Simoa (r=0.43, p=0.013). Multiple sclerosis (MS) patients had significantly higher serum NfL levels than controls when measured with Simoa (p=0.001) but not with the other platforms.Conclusions:We found Simoa to be more sensitive than ELISA or the ECL assay. Our results support the feasibility of quantifying NfL in serum; the results correlate with the more-established CSF NfL test. The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.

scholarly journals Neurofilament Light Chain and Cognitive Performance in Selected Siblings From the CATSLife Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 121-121
Author(s):  
Chandra Reynolds ◽  
Andrew Smolen ◽  
Christopher Link ◽  
Sally Wadsworth
Keyword(s):  
Cognitive Ability ◽  
Light Chain ◽  
Cognitive Aging ◽  
Neurological Diseases ◽  
Apoe Genotype ◽  
General Cognitive Ability ◽  
Healthy Individuals ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Case Status

Abstract Markers of neurodegeneration such as neurofilament light chain (NfL) may be elevated with neurological diseases such as multiple sclerosis (MS) as well as Alzheimer’s disease. NfL is a marker of axonal integrity where higher values positively relate to the degree of damage. NfL shows variations in early adulthood among healthy individuals and may relate to executive function performance in otherwise healthy individuals aged 19-32 years. In the ongoing CATSLife (Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging) Quanterix Simoa assays of NfL were measured in 34 individuals selected based on self-reported neuroinflammatory conditions (N = 5) or by APOE genotype (N_nonE4 = 18, N_E4 = 16). The distribution of NfL was consistent with other studies of early-mid adulthood (range = 1.3 - 22.3 pg/ml). Based on partial regression weights predicting log-transformed NfL, NfL was higher in cases (exp(b)=1.08 pg/ml), in males (exp(b)=1.25 pg/ml), by age (exp(b)=1.03 pg/ml per year) and in APOE E4 carriers (exp(b)=1.11 p/mg). Moreover, correlations partialed for age, sex, APOE e4 and case status suggest higher NfL may be associated with lower Full Scale IQ and general cognitive ability (r’s = -.18 and -. 28) overall and may be more evident among APOE E4 carriers (r’s = -.42 - .44, partialed for age, sex, case status). In this pilot study, the observed NfL associations with general cognitive ability, particularly among APOE E4 carriers, suggests NfL may be a salient biomarker of cognitive functioning by early- to mid-adulthood.

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