Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury

Abstract Little is known about the long-term consequences of anorexia nervosa (AN) in terms of possible brain neuronal injury. We aimed at investigating whether women with adolescent-onset AN exhibit increased serum levels of neurofilament light chain protein (NfL), a biomarker for neuronal injury, compared with matched controls at 30-year follow-up. Blood samples were collected from 34 women with adolescent-onset AN and 38 matched healthy comparison women (COMP), at a mean age of 44 years (range 38–48 years). NfL was measured in serum using the in-house single molecule array (Simoa) method. The individuals were asked whether they or their parents had been diagnosed with dementia. The Swedish National Patient Register was searched for diagnoses related to dementia. Serum NfL concentrations were significantly higher in the AN group (AN 27.7 pg/ml; COMP 19.0 pg/ml; p = 0.041). When individuals with medical/neurological disorders in the AN and COMP groups were excluded, there was a statistically non-significant trend towards higher concentrations in the AN group (AN 27.4 pg/ml; COMP 18.8 pg/ml; p = 0.060). None of the participants had been diagnosed with dementia. There was no significant correlation between serum NfL and AN duration (r = 0.15). There was a moderate negative correlation between the serum NfL concentration and the current BMI in the AN group (r = 0.44). This is the first time that serum NfL has been assessed in middle-aged women with a history of adolescent-onset AN. The results suggest that there might be increased axonal degeneration as a sequel of AN. Individuals remaining underweight had higher serum NfL concentrations than those with a normal/high BMI. Additional studies are needed to confirm increased serum NfL concentrations in individuals recovered from AN. There is a need for further study of axonal degeneration as a consequence of AN.

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Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

Journal of Neuroinflammation ◽

10.1186/s12974-020-01966-3 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Ngoc Dung Le ◽

Lukas Muri ◽

Denis Grandgirard ◽

Jens Kuhle ◽

David Leppert ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Single Molecule ◽

Light Chain ◽

Pneumococcal Meningitis ◽

Neuronal Damage ◽

Neuronal Injury ◽

Health Concern ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Inflammatory Phase

Abstract Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

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Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod

Multiple Sclerosis Journal ◽

10.1177/1352458517715132 ◽

2017 ◽

Vol 24 (8) ◽

pp. 1046-1054 ◽

Cited By ~ 73

Author(s):

Fredrik Piehl ◽

Ingrid Kockum ◽

Mohsen Khademi ◽

Kaj Blennow ◽

Jan Lycke ◽

...

Keyword(s):

Single Molecule ◽

Light Chain ◽

Detection Threshold ◽

Therapy Response ◽

Serum Levels ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Post Marketing ◽

Highly Correlated ◽

Ms Therapy

Background: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). Objective: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. Methods: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). Results: Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10−6), and levels remained stable at 24 months (13.2 (6.2)). Conclusion: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.

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Neurofilament light chain predicts disease activity in relapsing-remitting MS

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000422 ◽

2017 ◽

Vol 5 (1) ◽

pp. e422 ◽

Cited By ~ 46

Author(s):

Kristin N. Varhaug ◽

Christian Barro ◽

Kjetil Bjørnevik ◽

Kjell-Morten Myhr ◽

Øivind Torkildsen ◽

...

Keyword(s):

Disease Activity ◽

Single Molecule ◽

Light Chain ◽

Interferon Beta ◽

Serum Levels ◽

Serum Samples ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

T2 Lesions ◽

Relapsing Remitting

Objective:To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).Methods:A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.Results:NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.Conclusion:Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.ClinicalTrials.gov identifier:NCT00360906.

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Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-326914 ◽

2021 ◽

pp. jnnp-2021-326914

Author(s):

Dario Saracino ◽

Karim Dorgham ◽

Agnès Camuzat ◽

Daisy Rinaldi ◽

Armelle Rametti-Lacroux ◽

...

Keyword(s):

Single Molecule ◽

Light Chain ◽

Rate Of Change ◽

Longitudinal Change ◽

Youden Index ◽

Clinical Genetic ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Link Type ◽

Therapeutic Trials

ObjectiveNeurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.MethodsWe analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.ResultspNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.ConclusionsThis study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.Trial registration numbersNCT02590276 and NCT04014673.

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Serum levels of neurofilament light chain, neuron-specific enolase and S100 calcium-binding protein B during acute bacterial meningitis: a prospective cohort study

Infectious Diseases ◽

10.1080/23744235.2021.1883730 ◽

2021 ◽

pp. 1-11

Author(s):

Mads Hjortdal Grønhøj ◽

Tobias Sejbaek ◽

Rasmus Würgler Hansen ◽

Lykke Larsen ◽

Morten Dahl ◽

...

Keyword(s):

Cohort Study ◽

Bacterial Meningitis ◽

Light Chain ◽

Calcium Binding ◽

Neuron Specific Enolase ◽

Serum Levels ◽

Acute Bacterial Meningitis ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

S100 Calcium Binding Protein

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Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS

Multiple Sclerosis Journal ◽

10.1177/13524585211032348 ◽

2021 ◽

pp. 135245852110323

Author(s):

Jens Kuhle ◽

Nadia Daizadeh ◽

Pascal Benkert ◽

Aleksandra Maceski ◽

Christian Barro ◽

...

Keyword(s):

Single Molecule ◽

Light Chain ◽

Interferon Beta ◽

Efficacy And Safety ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Highly Active ◽

Sustained Reduction ◽

Relapsing Remitting ◽

Healthy Control

Background: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). Objective: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. Methods: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. Results: Baseline median sNfL levels were similar in alemtuzumab ( n = 354) and SC IFNB-1a–treated ( n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients ( n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). Conclusion: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. ClinicalTrials.gov identifier: NCT00530348, NCT00930553, NCT02255656

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Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD

Neurology ◽

10.1212/wnl.0000000000008160 ◽

2019 ◽

Vol 93 (13) ◽

pp. e1299-e1311 ◽

Cited By ~ 21

Author(s):

Mitsuru Watanabe ◽

Yuri Nakamura ◽

Zuzanna Michalak ◽

Noriko Isobe ◽

Christian Barro ◽

...

Keyword(s):

Disease Activity ◽

Single Molecule ◽

Multivariate Analyses ◽

Serum Levels ◽

Strongly Correlated ◽

Serum Samples ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Disability Status ◽

Spectrum Disorders

ObjectiveTo test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte and neuron filaments, respectively, are clinically useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorders (NMOSD).MethodsLevels of GFAP and NfL in serum (sGFAP and sNfL, respectively) and in CSF samples were measured in healthy controls (HCs) (n = 49; 49 serum samples), patients with NMOSD (n = 33; 42 CSF and 102 serum samples), and patients with multiple sclerosis (MS) (n = 49; 53 CSF and 91 serum samples) by ultrasensitive single-molecule array assays. Association of sGFAP and sNfL levels with clinical parameters was determined.ResultsFor both GFAP and NfL, CSF and serum levels were strongly correlated. Both were higher in the serum of patients with NMOSD than in HCs (both p < 0.001). Moreover, sGFAP was higher in NMOSD than in MS (median 207.7 vs 121.1 pg/mL, p < 0.001). In NMOSD, sGFAP concentration increased after recent relapse (540.9 vs 152.9 pg/mL, p < 0.001). Multivariate analyses indicated that sGFAP and sNfL were associated with Expanded Disability Status Scale score in NMOSD (p = 0.026 and p < 0.001, respectively). Higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS with a sensitivity of 73.0% and a specificity of 75.8%.ConclusionssGFAP and sNfL are likely to be good biomarkers of disease activity and disability, and the sGFAP/sNfL quotient at relapse is a potential diagnostic marker for NMOSD.

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

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217317743098 ◽

2017 ◽

Vol 3 (4) ◽

pp. 205521731774309 ◽

Cited By ~ 4

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.

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