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

Siller, Nelly; Kühle, Jens; Muthuraman, Muthuraman; Barro, Christian; Uphaus, Timo; Groppa, Sergiu; Kappos, Ludwig; Zipp, Frauke; Bittner, Stefan

doi:10.1177/1352458518765666

Cited by 177 publications

(197 citation statements)

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“…Of particular interest is the proof that sNfL levels can be used to separate not only patients with MS from healthy controls but also to separate patients with MS with and without persistent clinical and subclinical MRI disease activity. 19,29,30 In previous studies, increased sNfL levels in patients with MS have been independently associated with disability and relapse status and suggested to be a predictive marker for future relapses and disability worsening. 17,19 Further data have proved that patients on disease-modifying treatment had lower sNfL levels than untreated patients.…”

Section: Discussionmentioning

confidence: 98%

“…19,29,30 In previous studies, increased sNfL levels in patients with MS have been independently associated with disability and relapse status and suggested to be a predictive marker for future relapses and disability worsening. 17,19 Further data have proved that patients on disease-modifying treatment had lower sNfL levels than untreated patients. 29 In this line, another study found that patients who switched from injectable therapies to fingolimod had significantly lower sNfL levels than staying on injectables.…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have evaluated the relationship of sNfL levels with clinical and MRI data at the group level. 11,19,29 Only a few reports are available that assess sNfL levels during follow-up, but using low-frequency assessment periods of a year. 11,31 Our high-frequency sNfL assessment is capable to document the dynamics of sNfL peaks as increases for a short time period of 3-6 months, which are associated with disease activity.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggest serum (s)NfL as a potential predictive marker for MS disease outcome. 13,[17][18][19] Nevertheless data and studies are missing that clarify how sNfL measurements develop over time, at relapse, or remission and whether sNfL level may be able to predict treatment response.…”

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confidence: 99%

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Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.MethodsWe investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.ResultsBefore ATZ, sNfL was significantly increased in correlation with previous relapse/MRI activity. After ATZ, sNfL decreased quickly within the first 6 months. In patients classified as NEDA-3, sNfL declined and persisted at an individual low steady-state level of <8 pg/mL. During follow-up, 34 sNfL peaks with a >20 fold increase could be detected, which were associated with clinical or MRI disease activity. Even patient-reported relapse-suspicious symptoms, which have not been confirmed because relapses were accompanied by sNfL, increase, proposing sNfL assessment as a marker for relapse activity. sNfL started to increase earliest 5 months before, peaked at clinical onset, and recovered within 4–5 months. sNfL presented at higher levels in active patients requiring ATZ retreatment compared with responder patients. During 2 documented pregnancies, sNfL was at a low level, whereas a postpartum transient sNfL increase was seen without any signs of activity.ConclusionsThis study applied a long-term high-frequency sNfL assessment in an ATZ-treated cohort, allowing a holistic profiling on the individual level and highlighted that sNfL can eminently complement the individual clinical and MRI monitoring in clinical practice.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Akgün

Kretschmann

Haase

et al. 2019

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

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“…Elevated neurofilament light chain (NfL) is a more recently discovered biomarker of neurodegenerative diseases, including AD, frontotemporal dementia, amyotrophic lateral sclerosis, and multiple sclerosis (Chatterjee et al, 2018;Gille et al, 2018;Goossens et al, 2018;Siller et al, 2018). An increase in NfL in CSF and blood is interpreted as an indication of ongoing axonal damage (Lee, Taghian, & Petratos, 2014).…”

Section: Neurofilament Light Chainmentioning

confidence: 99%

The β‐secretase (BACE) inhibitor NB‐360 in preclinical models: From amyloid‐β reduction to downstream disease‐relevant effects

Neumann

Machauer

Shimshek

2019

British J Pharmacology

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Inhibition of β‐secretase 1 (BACE‐1; also known as β‐site amyloid precursor protein‐cleaving enzyme‐1) is a current approach to fight the amyloid‐β (Aβ) deposition in the brains of patients with Alzheimer's disease, and a number of BACE‐1 inhibitors are being tested in clinical trials. The BACE‐1 inhibitor NB‐360, although not a clinical compound, turned out to be a valuable pharmacological tool to investigate the effects of BACE‐1 inhibition on the deposition of different Aβ species in amyloid precursor protein (APP) transgenic mice. Furthermore, chronic animal studies with NB‐360 revealed relationships between BACE‐1 inhibition, Aβ deposition, and Aβ‐related downstream effects on neuroinflammation, neuronal function, and markers of neurodegeneration. NB‐360 effects on the processing of physiological BACE‐1 substrates as well as on nonenzymatic BACE‐1 functions have been investigated, complementing studies in BACE‐1 knockout mice. Because NB‐360 is also an inhibitor for BACE‐2, nonclinical studies in adult animals revealed physiological effects of BACE‐2 inhibition. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Association of Serum Neurofilament Light Levels With Long-term Brain Atrophy in Patients With a First Multiple Sclerosis Episode

et al. 2020

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IMPORTANCE Data are needed on the potential long-term prognostic association of serum neurofilament light in multiple sclerosis (MS). OBJECTIVE To evaluate serum neurofilament light as a biomarker associated with long-term disease outcomes in clinically isolated syndrome. DESIGN, SETTING, AND PARTICIPANTS This post hoc cohort study used data from the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, a 36-month, multicenter, placebocontrolled interferon β-1a randomized clinical trial conducted from April 1996 to March 2000, and its long-term (5-and 10-year) extension study from February 2001 to March 2009. Participants included individuals with a symptomatic initial demyelinating event and brain magnetic resonance imaging (MRI) lesions suggestive of MS. Data were analyzed from April 2017 through 2019. EXPOSURE The variable of interest was naturally occurring serum neurofilament light concentration MAIN OUTCOMES AND MEASURES Gadolinium-enhancing (Gd +) lesion number, T2 lesion volume, and brain parenchymal fraction, a measure of brain atrophy were measured at baseline and 5 and 10 years. Multivariate regression models evaluated whether age, sex, and baseline covariates, including serum neurofilament light, brain parenchymal fraction, Expanded Disability Status Scale, Gd + lesion count, and T2 lesion volume, were associated with brain parenchymal fraction changes over 5 and 10 years. RESULTS Among 308 included participants (mean [SD] age, 33.2 [7.6] years; 234 [76.0%] women), baseline serum neurofilament light concentrations were associated with Gd + lesions (Spearman r = 0.41; P < .001) and T2 lesion volume (Spearman r = 0.42; P < .001). Among covariates for brain parenchymal fraction change, serum neurofilament light concentration had the greatest correlation with change in brain parenchymal fraction at 5 years

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

Abstract: 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.

Cited by 177 publications

References 20 publications

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS

The β‐secretase (BACE) inhibitor NB‐360 in preclinical models: From amyloid‐β reduction to downstream disease‐relevant effects

Association of Serum Neurofilament Light Levels With Long-term Brain Atrophy in Patients With a First Multiple Sclerosis Episode

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