Neurofilaments contribution in clinic: state of the art

Delaby, Constance; Bousiges, Olivier; Bouvier, Damien; Fillée, Catherine; Fourier, Anthony; Mondésert, Etienne; Nezry, Nicolas; Omar, Souheil; Quadrio, Isabelle; Rucheton, Benoît; Schraen‐Maschke, Susanna; Pesch, Vincent Van; Vicca, Stéphanie; Lehmann, Sylvain; Bedel, Aurélie

doi:10.3389/fnagi.2022.1034684

Cited by 16 publications

(12 citation statements)

References 168 publications

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“…NfL is released into the cerebrospinal fluid (CSF) and blood upon axon injury [ 8 ]. Although being a sensitive indicator for axon damage and neuron death [ 40 ], plasma NfL was reported to increase under various conditions other than neurodegenerative diseases. Blood NfL concentration were reported to be correlated with various factors including BMI, age, diabetes, hypertension, dyslipidemia, and renal function [ 10 , 12 , 17 , 18 , 20 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Wu,

Xiao,

Wang

et al. 2024

Alz Res Therapy

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Background The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. Methods Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. Results The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = − 0.19, 95% CI − 0.224 to − 0.156, P < 0.001; B = − 0.009, 95% CI − 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = − 0.010, 95% CI − 0.133 to − 0.068, P < 0.001), but not with P-tau181 (B = − 0.003, 95% CI − 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = − 0.790, 95% CI − 1.026 to − 0,554, P < 0.001). Conclusions Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

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Section: Discussionmentioning

confidence: 99%

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Wu,

Xiao,

Wang

et al. 2024

Alz Res Therapy

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“…NfL is released into the cerebrospinal uid (CSF) and blood upon axon injury [8]. Although being a sensitive indicator for axon damage and neuron death [34], plasma NfL was reported to increase under various conditions other than neurodegenerative diseases. Blood NfL concentrations were reported to be correlated with various factors including BMI, age, diabetes, hypertension, dyslipidemia, and renal function [10,12,16,35,36].…”

Section: Discussionmentioning

confidence: 99%

Glomerular filtration rate, neurofilament light, and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Wang

Xiao

Wang

et al. 2023

Preprint

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Background The blood-based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. Methods Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. Results The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = -0.19, 95%CI -0.224 to -0.156, P < 0.001; B = -0.009, 95%CI -0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = -0.010, 95%CI -0.133 to -0.068, P < 0.001), but not with P-tau181 (B = -0.003, 95%CI -0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = -0.790, 95%CI -1.026 to -0,554, P < 0.001). Conclusions Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

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“…NfL is a protein located in the neuronal cytoskeleton and is released into the interstitial fluid (ISF) of the brain upon axonal damage or degeneration. Mainly in the field of neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, but also in other neurological disorders, such as multiple sclerosis and traumatic brain injury, there is already significant evidence for NfL as a blood‐based biomarker 8,9 . We hypothesize that NfL could also be useful in the management of epilepsy.…”

Section: Introductionmentioning

confidence: 93%

“…Mainly in the field of neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, but also in other neurological disorders, such as multiple sclerosis and traumatic brain injury, there is already significant evidence for NfL as a blood-based biomarker. 8,9 We hypothesize that NfL could also be useful in the management of epilepsy. Already in the 1990s, one group reported the altered expression of (non-)phosphorylated neurofilaments in a kainic acid rat model using immunohistochemistry on brain slices.…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light chain: A possible fluid biomarker in the intrahippocampal kainic acid mouse model for chronic epilepsy?

Custers,

Vande Vyver,

Kaltenböck

et al. 2023

Epilepsia

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ObjectiveIn the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the evaluation of treatment responsiveness. In this regard, biochemical traceability in biofluids is notably absent in contrast to other diseases. In the present preclinical study, we investigated the potential of neurofilament light chain (NfL) as a possible diagnostic and response fluid biomarker for epilepsy.MethodsWe gained insights into NfL levels during the various phases of the intrahippocampal kainic acid mouse model of temporal lobe epilepsy—namely, the status epilepticus (SE) and the chronic phase with spontaneous seizures. To this end, NfL levels were determined directly in the cerebral interstitial fluid (ISF) with cerebral open flow microperfusion as sampling technique, as well as in cerebrospinal fluid (CSF) and plasma. Lastly, we assessed whether NfL levels diminished upon curtailing SE with diazepam and ketamine.ResultsNfL levels are higher during SE in both cerebral ISF and plasma in kainic acid‐treated mice compared to sham‐injected mice. Additionally, ISF and plasma NfL levels are lower in mice treated with diazepam and ketamine to stop SE compared with the vehicle‐treated mice. In the chronic phase with spontaneous seizures, higher NfL levels could only be detected in ISF and CSF samples, and not in plasma. No correlations could be found between NfL levels and seizure burden, nor with immunohistological markers for neurodegeneration/inflammation.SignificanceOur findings demonstrate the translational potential of NfL as a blood‐based fluid biomarker for SE. This is less evident for chronic epilepsy, as in this case higher NfL levels could only be detected in ISF and CSF, and not in plasma, acknowledging the invasive nature of CSF sampling in chronic epilepsy follow‐up.

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Neurofilaments contribution in clinic: state of the art

Cited by 16 publications

References 168 publications

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Glomerular filtration rate, neurofilament light, and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

Neurofilament light chain: A possible fluid biomarker in the intrahippocampal kainic acid mouse model for chronic epilepsy?

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