Relationship between serum neurofilament light chain levels and cognitive decline over 9-years follow-up in patients after first demyelinating event suggestive of MS

2018 ◽  
Author(s):  
Tomas Uher ◽  
Dana Horakova
Keyword(s):  
Cognitive Decline ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Nuole Zhu ◽  
Miguel Santos-Santos ◽  
Ignacio Illán-Gala ◽  
Victor Montal ◽  
Teresa Estellés ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Cognitive Decline ◽  
Frontotemporal Dementia ◽  
Cortical Thickness ◽  
Light Chain ◽  
Diagnostic Performance ◽  
Acidic Protein ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract Background Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and their clinical utility in predicting disease progression. Methods pGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline  through group comparisons by tertile. Results Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005). Conclusions pGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

scholarly journals Neurofilament light chain related to longitudinal decline in frontotemporal lobar degeneration

2020 ◽  
pp. 10.1212/CPJ.0000000000000959
Author(s):  
Jiasi Vicky Zhang ◽  
David J. Irwin ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Edward B. Lee ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Light Chain ◽  
Frontotemporal Lobar Degeneration ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cognitive Domains ◽  
Diagnosis And Prognosis ◽  
Language Measures ◽  
Disease Modifying Treatment

ABSTRACTBackground:Accurate diagnosis and prognosis of frontotemporal lobar degeneration (FTLD) during life is an urgent concern in the context of emerging disease-modifying treatment trials. Few cerebrospinal fluid (CSF) markers have been validated longitudinally in patients with known pathology, and we hypothesized that CSF neurofilament light chain (NfL) would be associated with longitudinal cognitive decline in patients with known FTLD-TDP pathology.Methods:This case-control study evaluated CSF NfL, total-tau (tTau), phosphorylated-tau (pTau) and beta-amyloid (Aβ42) in known FTLD-Tau or FTLD-TDP pathology (n=50) and healthy controls (n=65), and an extended cohort of clinically-diagnosed patients with likely FTLD-Tau or FTLD-TDP (n=148). Regression analyses related CSF analytes to longitudinal cognitive decline (follow up ∼1 year), controlling for demographic variables and core AD CSF analytes.Results:In FTLD-TDP with known pathology, CSF NfL is significantly elevated compared to controls, and significantly associated with longitudinal decline on specific executive and language measures, after controlling for age, disease duration, and core AD CSF analytes. Similar findings are found in the extended cohort also including clinically-identified likely FTLD-TDP. While CSF NfL is elevated in FTLD-Tau compared to controls, the association between NfL and longitudinal cognitive decline is limited to executive measures.Conclusion:CSF NfL is associated with longitudinal clinical decline in relevant cognitive domains in patients with FTLD-TDP after controlling for demographic factors and core AD CSF analytes, and may also be related to longitudinal decline in executive functioning in FTLD-Tau.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012632
Author(s):  
Kjetil Bjornevik ◽  
Eilis J. O'Reilly ◽  
Samantha Molsberry ◽  
Laurence N. Kolonel ◽  
Loic Le Marchand ◽  
...  
Keyword(s):  
Light Chain ◽  
Conditional Logistic Regression ◽  
Disease Diagnosis ◽  
Health Study ◽  
Plasma Samples ◽  
Blood Draw ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Rate Ratios

Objective:To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations.Methods:We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels.Results:Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments.Conclusions:Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease.Classification of Evidence:This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

scholarly journals CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

2020 ◽  
Vol 7 (6) ◽  
pp. e880 ◽  
Author(s):  
Saúl Reyes ◽  
Ide Smets ◽  
David Holden ◽  
Karina Carrillo-Loza ◽  
Tatiana Christmas ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Oral Disease ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Treatment Escalation

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

scholarly journals Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

2021 ◽  
pp. 1-7
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

scholarly journals Serum neurofilament light chain as outcome marker for intensive care unit patients

2020 ◽  
Author(s):  
Anna Lena Fisse ◽  
Kalliopi Pitarokoili ◽  
David Leppert ◽  
Jeremias Motte ◽  
Xiomara Pedreiturria ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Central Nervous System ◽  
Nervous System ◽  
Intensive Care ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Icu Patients ◽  
Neurofilament Light ◽  
The Central Nervous System

Abstract Objective Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. Methods Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. Results NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). Conclusion NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.

scholarly journals Evaluation of plasma tau and neurofilament light chain biomarkers in a 12-year clinical cohort of human prion diseases

2021 ◽  
Author(s):  
Andrew G. B. Thompson ◽  
Prodromos Anastasiadis ◽  
Ronald Druyeh ◽  
Ines Whitworth ◽  
Annapurna Nayak ◽  
...  
Keyword(s):  
Prion Disease ◽  
Functional Impairment ◽  
Light Chain ◽  
Unmet Needs ◽  
Prion Diseases ◽  
Control Groups ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Mutation Carriers

AbstractPrion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau and neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals with prion disease during a 12 year prospective clinical study, alongside healthy and neurological control groups. This provides an unprecedented opportunity to evaluate their potential as biomarkers. Plasma tau and NfL were increased across all prion disease types. For distinguishing sCJD from control groups including clinically-relevant “CJD mimics”, both show considerable diagnostic value. In sCJD, NfL was substantially elevated in every sample tested, including during early disease with minimal functional impairment and in all follow-up samples. Plasma tau was independently associated with rate of clinical progression in sCJD, while plasma NfL showed independent association with severity of functional impairment. In asymptomatic PRNP mutation carriers, plasma NfL was higher on average in samples taken within 2 years of symptom onset than in samples taken earlier. We present biomarker trajectories for nine mutation carriers healthy at enrolment who developed symptoms during follow-up. NfL started to rise as early as 2 years before onset in those with mutations typically associated with more slowly progressive clinical disease. This shows potential for plasma NfL as a “proximity marker”, but further work is needed to establish predictive value on an individual basis, and how this varies across different PRNP mutations. We conclude that plasma tau and NfL have potential to fill key unmet needs for biomarkers in prion disease: as a secondary outcome for clinical trials (NfL and tau); for predicting onset in at-risk individuals (NfL); and as an accessible test for earlier identification of patients that may have CJD and require more definitive tests (NfL). Further studies should evaluate their performance directly in these specific roles.

scholarly journals Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain

2021 ◽  
pp. 135245852110637
Author(s):  
Jae-Won Hyun ◽  
So Yeon Kim ◽  
Yeseul Kim ◽  
Na Young Park ◽  
Ki Hoon Kim ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Acidic Protein ◽  
Healthy Controls ◽  
Longitudinal Assessment ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

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