Neurofilament light chain concentration in an aging population

Ladang, Aurélie; Kovacs, Stéphanie; Lengelé, Laetitia; Locquet, Médéa; Reginster, Jean‐Yves; Bruyère, Olivier; Cavalier, Étienne

doi:10.1007/s40520-021-02054-z

Cited by 42 publications

(35 citation statements)

References 33 publications

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“…Consistent with our findings, two very recent studies also demonstrated the importance of renal function as a contributor to sNfL levels ( Koini et al, 2021 ; Ladang et al, 2022 ). While these studies featured smaller samples from normal aging cohorts, they further support the key conclusions of our study which examined a significantly larger sample of elderly patients with cardiovascular disease.…”

Section: Discussionsupporting

confidence: 93%

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation

et al. 2022

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ObjectiveSerum neurofilament light chain (sNfL) is increasingly used as a neuroaxonal injury biomarker in the elderly. Besides age, little is known about how other physiological factors like renal function and body mass index (BMI) alter its levels. Here, we investigated the association of estimated glomerular filtration rate (eGFR) and BMI with sNfL in a large sample of elderly patients with atrial fibrillation (AF).MethodsThis is a cross-sectional analysis from the Swiss-AF Cohort (NCT02105844). We measured sNfL using an ultrasensitive single-molecule array assay. We calculated eGFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine (eGFRcrea) and creatinine–cystatin C (eGFRcrea–cys) formulas, and BMI from weight and height measurements. We evaluated the role of eGFR and BMI as determinants of sNfL levels using multivariable linear regression and the adjusted R2 (R2adj).ResultsAmong 2,277 Swiss-AF participants (mean age 73.3 years), eGFRcrea showed an inverse curvilinear association with sNfL after adjustment for age and cardiovascular comorbidities. BMI also showed an independent, inverse linear association with sNfL. The R2adj of models with age, eGFRcrea, and BMI alone was 0.26, 0.35, and 0.02, respectively. A model with age and eGFRcrea combined explained 45% of the sNfL variance. Sensitivity analyses (i) further adjusting for vascular brain lesions (N = 1,402 participants with MRI) and (ii) using eGFRcrea–cys yielded consistent results.InterpretationIn an elderly AF cohort, both renal function and BMI were associated with sNfL, but only renal function explained a substantial proportion of the sNfL variance. This should be taken into account when using sNfL in elderly patients or patients with cardiovascular disease.

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Section: Discussionsupporting

confidence: 93%

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation

et al. 2022

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“…Nonetheless, while CSF NfL levels are principally influenced by the location and the extent of the injury [ 242 ], blood NfL levels may also be affected by the integrity of the blood-brain barrier (BBB) [ 243 ], PNS damage [ 244 , 245 ], cardiovascular risk factors [ 246 ], impaired renal function [ 247 ] and increased blood volume [ 248 , 249 ]. Additionally, low concentrations of NfL can be constantly detected in different body fluids, suggesting that NfL is released into CSF and blood as part of physiological processes, such as ageing [ 247 , 250 , 251 ], ageing-related neurodegeneration and loss of BBB integrity [ 252 , 253 ].…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Biernacki

Kokas

Sandi

et al. 2022

IJMS

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Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient’s health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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“…This age-specific increase was recently determined in healthy individuals as a 2.2% rise per year in blood NfL levels 255 . Furthermore, decreasing renal function associated with the elderly might also influence blood NfL concentrations [256][257][258] . Thus, this factor should also be considered when interpreting NfL levels.…”

Section: Neurofilament Proteins -Backgroundmentioning

confidence: 99%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

Biernacki¹,

Kokas²,

Sandi³

et al. 2022

Preprint

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Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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Neurofilament light chain concentration in an aging population

Cited by 42 publications

References 33 publications

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

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