Serum neurofilament light

Tiedt, Steffen; Duering, Marco; Barro, Christian; Kaya, Asli Gizem; Boeck, J; Bode, Felix J; Klein, Matthias; Dorn, Franziska; Gesierich, Benno; Kellert, Lars; Ertl‐Wagner, Birgit; Goertler, Michael; Petzold, Gabor C.; Kuhle, Jens; Wollenweber, Frank Arne; Peters, Nils; Dichgans, Martin

doi:10.1212/wnl.0000000000006282

Cited by 159 publications

(113 citation statements)

References 48 publications

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“…Results from MS populations have shown that increased levels of NfL in the CSF or blood were related to greater WM hyperintensity (WMH) volumes and gadolinium enhancing lesions ( Chitnis et al, 2018 ; Dalla Costa et al, 2019 ; Disanto et al, 2017 ; Kuhle et al, 2019 ). A similar pattern was found in patients with ischemic stroke ( Tiedt et al, 2018 ) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) ( Gravesteijn et al, 2019 ). Diffusion tensor imaging (DTI) is a particular form of diffusion-weighted imaging that characterizes the movement of water molecules in the brain and provides a way to examine microstructural changes of WM integrity.…”

Section: Introductionsupporting

confidence: 70%

“…In addition to such overt damage, microstructural changes in WM can be assayed using DTI. There have been inconsistent results establishing whether CSF and blood levels of NfL are sensitive to such microstructural changes in WM detectable using DTI ( Menke et al, 2015 ; Mielke et al, 2019 ; Moore et al, 2018 ; Racine et al, 2019 ; Tiedt et al, 2018 ). When examining baseline DTI data using voxel-wise- and ROI-based approaches in MC we found that higher levels of serum NfL were negatively associated with FA, and positively associated with MD, RD, and DA throughout the entire cortex, although effects were strongest in posterior regions ( Table 2 and Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

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Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Schultz

Strain

Adedokun

et al. 2020

Neurobiology of Disease

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Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset ( N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.

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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Schultz

Strain

Adedokun

et al. 2020

Neurobiology of Disease

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“…However, following adjustment, the authors did not find a correlation between serum NF-L and infarct size on admission or mRS at 3 months. Tiedt et al (12) found NF-L levels to be increased in ischemic stroke patients at admission (<24 h), days 2, 3, and 7, and at 3 and 6 months post-stroke, with peak levels at day 7. NF-L levels at day 7 correlated with infarct volumes assessed by MRI and with mRS 3 months post-stroke, but after adjustment for age and hypertension, only NF-L levels obtained on days 3 and 7 correlated with infarct volume.…”

Section: Discussionmentioning

confidence: 98%

“…The inflammatory process that ensues after a stroke destabilizes the blood-brain barrier (BBB) and contributes to neuro-axonal damage, thereby increasing the release of NFs and glial and inflammatory markers into the CSF and blood (11). Ischemic stroke has recently been shown to cause persistent elevations in serum NF-L that correlated with infarct volumes and recurrent ischemic lesions (12). Furthermore, NF-L levels obtained within 24 h of symptom onset in the blood of ischemic stroke and TIA patients were associated with clinical severity on admission and TIA diagnosis, but not with infarct size or functional outcome at 3 months (13).…”

Section: Introductionmentioning

confidence: 99%

Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients

et al. 2020

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Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3-to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Nielsen et al. Acute Plasma NF-L Levels in Stroke Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.

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“…NF-L serum levels are higher in ischemic stroke cases than in healthy controls, while also differentiating between ischemic stroke and transient ischemic attack (Table 1). Higher NF-L levels were associated with more severe disability scores [44,45]. In a large prospective study, Pedersen et al used Simoa to study the association between functional outcome and serum NF-L levels sampled within the first 1-14 days, 3 months, and 7 years after ischemic stroke [41].…”

Section: Strokementioning

confidence: 99%

Neurofilaments: The C-Reactive Protein of Neurology

et al. 2020

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Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.

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Serum neurofilament light

Abstract: Serum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.

Cited by 159 publications

References 48 publications

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients

Neurofilaments: The C-Reactive Protein of Neurology

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