Neurofilament light chain serum levels reflect disease severity in MOG-Ab associated 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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Plasma glial fibrillary acidic protein and neurofilament light chain are measures of disease severity in semantic variant primary progressive aphasia

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-325085 ◽

2020 ◽

pp. jnnp-2020-325085

Author(s):

Carolin Heller ◽

Elise Chan ◽

Martha S Foiani ◽

Emily Todd ◽

Lucy L Russell ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Disease Severity ◽

Light Chain ◽

Primary Progressive Aphasia ◽

Acidic Protein ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Progressive Aphasia ◽

Primary Progressive ◽

Semantic Variant

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

European Child & Adolescent Psychiatry ◽

10.1007/s00787-020-01657-7 ◽

2020 ◽

Author(s):

Elisabet Wentz ◽

Sandra Rydberg Dobrescu ◽

Lisa Dinkler ◽

Carina Gillberg ◽

Christopher Gillberg ◽

...

Keyword(s):

Anorexia Nervosa ◽

Single Molecule ◽

Light Chain ◽

Axonal Degeneration ◽

Neuronal Injury ◽

Serum Levels ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

National Patient ◽

History Of

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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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 Severity and Progression in Multiple System Atrophy

Movement Disorders ◽

10.1002/mds.28847 ◽

2021 ◽

Author(s):

Lingyu Zhang ◽

Bei Cao ◽

Yanbing Hou ◽

Xiaojing Gu ◽

Qianqian Wei ◽

...

Keyword(s):

Multiple System Atrophy ◽

Disease Severity ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light

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High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000598 ◽

2019 ◽

Vol 6 (5) ◽

pp. e598 ◽

Cited By ~ 13

Author(s):

Simon Thebault ◽

Daniel R. Tessier ◽

Hyunwoo Lee ◽

Marjorie Bowman ◽

Amit Bar-Or ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Disease Severity ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Hematopoietic Stem

ObjectiveTo evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- and post-treatment with immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) and examine associations with clinical and MRI outcomes.MethodsPaired serum and CSF in addition to MRI and clinical measures were collected on 23 patients with MS at baseline and 1 and 3 years post-IAHSCT. An additional 33 sera and CSF pairs were taken from noninflammatory neurologic controls. NfL levels were quantitated using the Simoa platform (Quanterix).ResultsBaseline MS NfL levels were significantly elevated relative to controls in serum (p = 0.001) and CSF (p = 0.001). Following IAHSCT, high pretreatment NfL levels significantly reduced in serum (p = 0.0023) and CSF (p = 0.0068) and were not significantly different from controls. Serum and CSF NfL levels highly correlated (r = 0.81, p < 0.0001). Baseline NfL levels were associated with worse pretreatment disease measures (Expanded Disability Status Scale [EDSS], relapses, MRI lesions, and MR spectroscopy (MRS) N-acetylaspartate/creatine). Elevated baseline NfL levels were associated with persistently worse indices of disease burden post-IAHSCT (sustained EDSS progression, cognition, quality of life, T1 and T2 lesion volumes, MRS, and brain atrophy).ConclusionThese data substantiate that serum and CSF NfL levels reflect disease severity and treatment response in patients with MS and may therefore be a useful biomarker. Baseline serum levels associated with markers of pretreatment disease severity and post-treatment outcomes.Classification of evidenceThis study provides Class II evidence that for patients with aggressive MS, serum NfL levels are associated with disease severity.

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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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CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP

Neurology ◽

10.1212/wnl.0000000000004859 ◽

2017 ◽

Vol 90 (4) ◽

pp. e273-e281 ◽

Cited By ~ 31

Author(s):

Julio C. Rojas ◽

Jee Bang ◽

Iryna V. Lobach ◽

Richard M. Tsai ◽

Gil D. Rabinovici ◽

...

Keyword(s):

Disease Progression ◽

Disease Severity ◽

Light Chain ◽

Rating Scale ◽

Superior Cerebellar Peduncle ◽

Phosphorylated Tau ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Phosphorylated Tau 181 ◽

Predict Disease Progression

ObjectiveTo determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP).MethodsWe compared the ability of baseline CSF β-amyloid1–42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients.ResultsHigher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS (p = 0.004, false discovery rate–corrected) and SEADL (p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS (p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL (p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau (p = 0.003) or NfL (p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively).ConclusionsBoth CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease.

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Plasma neurofilament light chain concentration in the inherited peripheral neuropathies

Neurology ◽

10.1212/wnl.0000000000004932 ◽

2018 ◽

Vol 90 (6) ◽

pp. e518-e524 ◽

Cited By ~ 61

Author(s):

Åsa Sandelius ◽

Henrik Zetterberg ◽

Kaj Blennow ◽

Rocco Adiutori ◽

Andrea Malaspina ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Disease Severity ◽

Light Chain ◽

Cross Sectional Study ◽

Healthy Controls ◽

Neurofilament Light Chain ◽

Cross Sectional ◽

Neurofilament Light ◽

Charcot Marie Tooth Disease ◽

Inherited Neuropathies

ObjectiveTo perform a cross-sectional study to determine whether plasma neurofilament light chain (NfL) concentration is elevated in patients with Charcot-Marie-Tooth disease (CMT) and if it correlates with disease severity.MethodsBlood samples were collected from 75 patients with CMT and 67 age-matched healthy controls over a 1-year period. Disease severity was measured using the Rasch modified CMT Examination and neuropathy scores. Plasma NfL concentration was measured using an in-house-developed Simoa assay.ResultsPlasma NfL concentration was significantly higher in patients with CMT (median 26.0 pg/mL) compared to healthy controls (median 14.6 pg/mL, p < 0.0001) and correlated with disease severity as measured using the Rasch modified CMT examination (r = 0.43, p < 0.0001) and neuropathy (r = 0.37, p = 0.044) scores. Concentrations were also significantly higher when subdividing patients by genetic subtype (CMT1A, SPTLC1, and GJB1) or into demyelinating or axonal forms compared to healthy controls.ConclusionThere are currently no validated blood biomarkers for peripheral neuropathy. The significantly raised plasma NfL concentration in patients with CMT and its correlation with disease severity suggest that plasma NfL holds promise as a biomarker of disease activity, not only for inherited neuropathies but for peripheral neuropathy in general.

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