Elevated NfL Research Articles

Increased serum NfL and GFAP levels indicate different subtypes of neurologic immune-related adverse events during treatment with immune checkpoint inhibitors.

Neurologic immune-related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate the diagnostic utility of serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty-three patients were included at three comprehensive cancer centers, of these 20 patients with manifest nirAEs and 11 patients with irHypophysitis. Controls included patients without any irAE (n = 8) and other irAEs (n = 14). Using a single-molecule enzyme-linked immunosorbent assay (Simoa), serum levels were measured prior to, during and after the manifestation of (n)irAEs in 80 samples. Symptom severity of the (n)irAEs was graded according to the Common Criteria for Adverse Events (CTCAE) version 5.0. Serum NfL levels were significantly higher in the nirAE group (n = 20) compared to irHypophysitis (n = 11; p = .0025) and controls (n = 22; p = .0384). Subgroup analysis demonstrated a significant elevation of NfL in nirAEs of the peripheral nerves (PNirAE) in contrast to neuromuscular syndromes (NMirAE) (p = .0260). GFAP levels were highest in patients with nirAE affecting the central nervous system (CNSirAE) compared to PNirAE and NMirAE (p = .0064). Symptom severity of nirAEs was associated with increased levels of NfL and GFAP (p = .0069, .0092). Individuals with elevated NfL levels exhibited less favorable outcomes of the (n)irAEs (p = .0199). Measurement of NfL and GFAP may be helpful for the differentiation of the broad spectrum of nirAEs and may serve as an indicator of symptom severity. Further investigation is needed to evaluate their potential as diagnostic and prognostic biomarkers.

Plastic harmful ingredients reduce the level of neurofilament light chain protein.

Population exposure to plastics is increasing, and plasticizers are frequently detected in humans as important ingredients of plastic products. However, patterns of exposure to harmful ingredients of plastics and their effects on neurofilament light chain (NFL), a marker of active brain pathology, are currently inconclusive. Herein, we employed a range of statistical methods to thoroughly investigate the impact of 24 plastic hazardous ingredients and their varying exposure patterns on NFL concentrations in the blood of the general population in 533 participants. Generalized linear model revealed a positive correlation between Mono-isononyl phthalate and Mono (2-Ethyl- 5-Hydroxyhexyl) Phthalate (MEHHP) with NFL. Furthermore, a significant dose-response relationship was observed between MEHHP and NFL, while Butyl paraben and Mono (Hydroxy-Isononyl) Ester exhibited a distinct "inverted U-shaped" nonlinear pattern with NFL. Additionally, Weighted Quantile Sum model allowed us to identify the mixed effects of all 24 plastic hazardous ingredients, with Mono(2-Ethyl-5-Oxohexyl) Phthalate, Mono-isobutyl phthalate, Mon butyl Phthalate, Propyl paraben and Triclosan occupying prominent positions. Finally, the latent profile analysis categorized exposures into high, medium, and low patterns, confirming that higher exposure to plastic hazardous ingredients posed a significant risk factor for elevated NFL levels in the blood. Exposure to plastic hazardous ingredients significantly increases the risk of NFL, the present contributes to early detection and intervention to reduce the incidence of neurodevelopmental disorder.

Neurofilament Light Protein as a Biomarker in Severe Mental Disorders: A Systematic Review

Severe mental disorders (SMDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD), are heterogeneous psychiatric diseases that impose a significant societal burden due to their chronic disabling nature. There are no objective and reliable diagnostic tests for SMDs; thus, there is an urgent need for specific biomarkers to improve diagnosis, treatment, and resource allocation. Neurofilaments, found in cerebrospinal fluid and blood, offer reliable diagnostic and prognostic potential. This review discusses the link between neurofilament light chain (NfL) involvement in psychiatric and neurodegenerative diseases and gives insights into the diagnostic and prognostic value of NfL in SMDs. This systematic review searched PubMed, Scopus, and Web of Science databases to answer the research question “Are NfL levels higher in individuals with SMDs compared to healthy controls?” using terms related to neurofilament, SMDs, SZ, BD, and depression. Of 8577 initial papers, 115 were relevant. After exclusions and manual additions, 17 articles were included. Studies indicate elevated NfL levels in SMDs compared to healthy controls, suggesting its potential as a biomarker for SMDs and for distinguishing neurodegenerative diseases from psychiatric disorders. However, further longitudinal research is needed to confirm its reliability for differential diagnosis, disease prediction, and treatment assessment in psychiatry.

Assessment of axonal injury in multiple sclerosis: combined analysis of serum light-chain neurofilaments and diffusion tensor imaging

BackgroundMultiple sclerosis (MS) is a chronic neuroinflammatory condition characterised by demyelination and axonal damage in the central nervous system. Diffusion tensor imaging (DTI) enables non-invasive investigation of microstructural white matter...

Point-of-Care Neurofilament Light Detection for Neurological Disease Monitoring

Neurofilament light chain (NfL) is a cytoplasmic protein predominantly found in neurons. Its primary role is to provide structural support to myelinated axons during their growth and maintenance. When axons are damaged due to injury or neurodegenerative processes, NfL levels increase in various bodily fluids, including the extracellular matrix, cerebrospinal fluid (CSF), and blood. The clinical significance of NfL lies in its association with neurological conditions. High levels of NfL have been observed in several contexts: Medical Emergencies: In acute medical emergencies such as stroke and head injuries, elevated NfL levels are detected. This rapid response makes NfL a potential biomarker for assessing acute neuronal damage.Neurodegenerative Diseases: Chronic neurodegenerative conditions, including multiple sclerosis (MS) and Alzheimer's disease, are characterized by progressive neuronal loss. NfL levels are significantly elevated in these diseases, reflecting ongoing axonal damage.Monitoring Neurodegeneration: Utilizing NfL as a monitoring tool has gained attention. Its presence in easily accessible bodily fluids (such as blood) makes it valuable for creating point-of-care mechanisms. By tracking NfL levels over time, clinicians can assess disease progression, treatment response, and overall neuronal health. Current NfL monitoring techniques such as Fourth-Generation Immunoassays (SIMOA or Quanterix). These highly sensitive assays allow quantification of NfL even at low levels. They are particularly useful for measuring NfL in plasma and serum. However, they require specialized equipment and trained personnel, limiting their widespread adoption. Microfluidic Cartridge-Based Automated Immunoassay Platforms such as ELLA have also been employed. While these platforms offer automated NfL measurement more conveniently, they also require expensive equipment and proper sample transportation.In this proposal, we introduce a novel Point-of-Care (PoC) mechanism designed for the rapid detection of Neurofilament Light Chain (NfL) in blood plasma. Our approach aims to eliminate the need for sample transportation, reduce procedural delays, and improve turnaround time. We have developed an Electrochemical Impedance Spectroscopy (EIS) platform specifically tailored for quantifying NfL levels within the physiological range in plasma. By leveraging the chemical interactions between the NfL antibody and antigen, we detect changes in impedance at the electrode-electrolyte interface as a factor of the chemical interaction. To validate our platform, we conducted spike and recovery experiments. These experiments illustrate the platform's ability to detect NfL in plasma samples reliably. In summary, our proposed PoC mechanism represents a significant advancement in NfL monitoring for neurodegenerative diseases. By combining accessibility, precision, and rapidity, we aim to enhance patient care and disease management.

Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review.

This narrative review explores the current landscape of blood biomarkers in Frontotemporal dementia (FTD). Neurofilament light chain (NfL) may be useful in the differentiation of behavioral variant FTD from primary psychiatric disorders (PPDs) or dementia with Lewy bodies (DLB). In prodromal FTD and presymptomatic mutation carriers (GRN, MAPT, C9orf72), elevated NfL may herald pheno-conversion to full-blown dementia. Baseline NfL correlates with steeper neuroanatomical changes and cognitive, behavioral and functional decline, making NfL promising in monitoring disease progression. Phosphorylated neurofilament heavy chain (pNfH) levels have a potential limited role in the demarcation of the conversion stage to full-blown FTD. Combined NfL and pNfH measurements may allow a wider stage stratification. Total tau levels lack applicability in the framework of FTD. p-tau, on the other hand, is of potential value in the discrimination of FTD from Alzheimer's dementia. Progranulin concentrations could serve the identification of GRN mutation carriers. Glial fibrillary acidic protein (GFAP) may assist in the differentiation of PPDs from behavioral variant FTD and the detection of GRN mutation carriers (additional research is warranted). Finally, TAR DNA-binding protein-43 (TDP-43) appears to be a promising diagnostic biomarker for FTD. Its potential in distinguishing TDP-43 pathology from other FTD-related pathologies requires further research.

Cumulative Socioeconomic Status Risk is Associated With Greater Increase in Serum Neurofilament Light Chain Levels Among Middle-Aged Black Adults.

This study examined the longitudinal relationship between cumulative socioeconomic status (SES) risk and serum neurofilament light chain (NfL) levels to better understand the association between social factors and a biomarker of neurodegeneration. We used data from the Family and Community Health Study, collecting psychosocial and blood data at 2 waves (2008) and (2019) from 254 Black Americans (43 males and 211 females). Blood samples were analyzed at each wave for serum NfL concentrations. Regression analysis and mixed-effect modeling examined relationships between cumulative SES risk and serum NfL, controlling for covariates and assessing time effects. Utilizing 11-year longitudinal data, serum NfL levels increased with age. Higher cumulative SES risk at baseline correlated with elevated serum NfL at the 11-year follow-up and predicted a greater increase in NfL levels. Clinically, NfL is a sensitive biomarker for axonal injury and neurodegeneration, commonly used to detect early and preclinical stages of conditions such as Alzheimer's disease, multiple sclerosis, and other neurodegenerative disorders. Our results suggest that exposure to cumulative SES risk among Black adults may contribute to elevated levels of NfL, indicating potential early neurodegeneration. Given the established role of NfL in detecting neurodegenerative processes, these findings underscore the importance of interventions that bolster social safety nets and social connectedness to enhance brain health and mitigate neurodegenerative risks.

Relationship between longer sleep and serum neurofilament light chain in american adults: evidence from the 2013–2014 US national health and nutrition examination survey

BackgroundSleep disturbance is linked to neurodegenerative diseases and the related brain pathophysiology. Serum neurofilament light chain (NfL) is a reliable biomarker for neurological disorders. This study examined the association between sleep characteristics and serum NfL levels in American adults.MethodsIn this cross-sectional study, data from the 2013–2014 US National Health and Nutrition Examination Survey were utilized. Participants were categorized into short (≤ 6 h), normal (7–8 h), and long (≥ 9 h) sleep groups based on their self-reported sleep durations. Sleep duration, trouble sleeping, and diagnosed sleep disorders were queried, forming “sleep pattern (healthy, moderate, and poor).” The association between sleep characteristics and serum NfL levels was assessed using multivariate linear regression models. Stratification and sensitivity analyses were conducted to determine the stability of results.ResultsOverall, 1637 participants were included; among them, 48.2% were male and 51.8% were female (mean ± SD, age: 46.9 ± 15.5 years) and 38.8% reported sleeping for ≤ 6 h, 54.4% for 7–8 h, and 6.8% for ≥ 9 h. Participants with longer sleep duration, poor sleep pattern, diagnosed sleep disorders, or trouble sleeping exhibited higher serum NfL levels. A positive correlation was found between extended sleep and elevated serum NfL levels (Adjusted β = 4.82, 95%CI: 2.2, 7.44, P < 0.001), with no significant correlation observed in the short-sleep group or those with poor sleep pattern. Stratified and sensitivity analyses confirmed the robustness of the relationship between longer sleep and elevated serum NfL levels.ConclusionsA long sleep duration is associated with higher serum NfL levels than a normal sleep duration in American adults.

Motor deficits and brain pathology in the Parkinson's disease mouse model hA53Ttg.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of α-synuclein (α-syn) aggregates. The A53T missense point mutation occurs in autosomal dominant familial PD and has been found to promote the aggregation of α-syn. To investigate the role of the A53T mutation in PD, researchers have developed various mouse models with this mutation. We therefore conducted a comprehensive characterization of the tg(THY1-SNCA*A53T)M53Sud mouse model (hA53Ttg mice) for its motor and pathological features. hA53Ttg mice were tested for motor impairments in a series of motor tests at 2, 4 or 6 months of age. Human α-syn and α-syn pSer129, as well as GFAP and Iba1 signal were labeled and quantified in the cortex, hippocampus, and brainstem. Neurofilament light chain (NF-L) levels were measured in the cerebrospinal fluid (CSF) and plasma. Ex vivo analyses were performed at the age of 2, 4, 6, and 10 months. Behavioral tests revealed early muscle weakness and motor impairments that progressed with age. Immunohistochemical analyses demonstrated elevated levels of human α-syn and α-syn pSer129 in all evaluated brain regions. α-syn pSer129 labeling further revealed fiber-like structures in the cortex of older animals. Neuroinflammation was observed in an age-dependent manner. Biochemical evaluation revealed elevated NF-L levels in the plasma and CSF. Overall, our findings highlight the value of hA53Ttg mice in modeling PD-associated pathologies that closely resemble those observed in PD patients. Our results thus suggest that hA53Ttg mice are a useful tool for studying the underlying mechanisms of PD.

Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson’s Disease

Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson’s disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years. Mixed-effects regression analyzed changes in NFL and the association with annual changes in MMSE and UPDRS-III scores over 10 years. PD patients had elevated serum NFL at all visits and a faster annual increase over 5 years compared to controls (0.09 pg/mL per year; p = 0.029). Higher baseline NFL predicted faster cognitive decline β −0.77 transformed MMSE; p = 0.010), and a 40% NFL increase predicted future motor decline (β 0.28 UPDRS-III; p = 0.004). Elevated serum NFL in early PD is linked to faster cognitive and motor impairment, suggesting its prognostic value in PD biomarker panels.

Progression predictors of clinically isolated syndrome to multiple sclerosis: A prospective study in China

ObjectivesClinically isolated syndrome (CIS) is a preclinical phase of multiple sclerosis (MS). The progression rate of CIS to clinical definite MS (CDMS) varies significantly across different populations, and identifying predictors of progression is crucial for early diagnosis and treatment. We aimed to investigate predictors of progression from CIS to CDMS in a Chinese cohort. MethodsA single-center cohort study was conducted with newly diagnosed patients with CIS in China between 2018 and 2021. All patients underwent a comprehensive clinical evaluation, including neurological examination, magnetic resonance imaging, and laboratory tests. Follow-up assessments were conducted at regular intervals to monitor disease progression. Progression to CDMS was defined according to the 2017 McDonald criteria. Age, sex, Expanded Disability Status Scale (EDSS) score, number of patients with magnetic resonance imaging gadolinium-enhancing (Gd+) lesions, T2 lesions and Gd+ lesions count, CSF cell count, CSF total protein, CSF and serum neurofilament light chain (NfL), progranulin (PGRN) and Th17-related cytokines (IL-6, IL-17, IL-21, IL-22, IL-23 and TGF-β) were measured for association with risk of progression to CDMS. ResultsA total of 96 CIS patients were recruited in the study. During the at least 24 months follow-up period, 57 (59.38 %) CIS patients progressed to CDMS, while 39 (40.62 %) patients without progression remained stable as CIS. Multivariate analysis revealed that younger age at onset (OR= 43.43, 95 % CI= 1.76–1071.68, p<0.021), higher CSF elevated protein (OR=58.64, 95 % CI=2.72–1264.51, p=0.009), higher CSF NfL levels (OR= 97.00, 95 % CI= 4.68–2012.99, p=0.003) and higher CSF IL-23 levels (OR= 412.02, 95 % CI=6.56–25869.60, p=0.004) were associated with high risk of progression to CDMS. ConclusionYounger age at onset, elevated CSF NfL, IL-23 and protein levels might be progression predictors of CIS to CDMS in Chinese population.

CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder

We investigated the biomarker profile of neurodegeneration, Alzheimer’s and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ42 and Aβ40), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ42/Aβ40 ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26–12.99), p = 0.019], mild cognitive impairment [3.86 (1.96–7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09–4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ42 was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ42 is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.

Plasma biomarkers of neurodegeneration in patients and high risk subjects with Lewy body disease

Comorbid Alzheimer’s disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled. Plasma amyloid-beta (Aβ) composite was measured using immunoprecipitation-mass spectrometry assays. Plasma phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and alpha-synuclein (aSyn) were measured using a single-molecule array. Plasma p-tau181 levels were higher in the PD and DLB groups than in the low-risk group. Aβ composite level was higher in the DLB group than in the high-risk group. AD-related biomarker levels were not elevated in the high-risk group. NfL levels were higher in the high-risk, PD, and DLB groups than in the low-risk group. In the PD group, Aβ composite was associated with cognitive function, p-tau181 with motor function and non-motor symptoms, and NfL with cognitive and motor functions and non-motor symptoms. In the high-risk group, NfL was associated with metaiodobenzylguanidine scintigraphy abnormalities. The PD and DLB groups exhibited comorbid AD neuropathology, though not in the prodromal phase. Elevated plasma NfL levels, even without elevated AD-related plasma biomarker levels, may indicate aSyn-induced neurodegeneration in the LBD prodromal phase.

An exploratory study of the damage markers NfL, GFAP, and t-Tau, in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease

There is growing evidence suggesting that immunological mechanisms play a significant role in the development of psychiatric symptoms in certain patient subgroups. However, the relationship between clinical red flags for suspected autoimmune psychiatric disease and signs of central nervous system (CNS) pathology (e.g., routine cerebrospinal fluid (CSF) alterations, CNS damage markers, neurophysiological or neuroimaging findings) has received limited attention. Here, we aimed to describe the prevalence and distribution of potential CNS pathologies in psychiatric patients in relation to clinical red flags for autoimmune psychiatric disease and psychiatric symptoms. CSF routine findings and CNS damage markers; neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP) and total Tau (t-Tau), in CSF from 127 patients with psychiatric disease preselected for suspected immunological involvement were related to recently proposed clinical red flags, psychiatric features, and MRI and EEG findings. Twenty-one percent had abnormal routine CSF findings and 27% had elevated levels of CNS damage markers. Six percent had anti-neuronal antibodies in serum and 2% had these antibodies in the CSF. Sixty-six percent of patients examined with MRI (n = 88) had alterations, mostly atrophy or nonspecific white matter lesions. Twenty-seven percent of patients with EEG recordings (n = 70) had abnormal findings. Elevated NfL levels were associated with comorbid autoimmunity and affective dysregulation symptoms. Elevated t-Tau was associated with catatonia and higher ratings of agitation/hyperactivity. Elevated GFAP was associated with acute onset, atypical presentation, infectious prodrome, tics, depressive/anxiety symptom ratings and overall greater psychiatric symptom burden. In conclusion, preselection based on suspected autoimmune psychiatric disease identifies a population with a high prevalence of CSF alterations suggesting CNS pathology. Future studies should examine the value of these markers in predicting treatment responses.

Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders.

Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders. We recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy. A total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03). An elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.

Elevated serum neurofilament light chain levels are associated with hepatic encephalopathy in patients with cirrhosis.

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms. Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = -0.42; p ≤ 0.001), verbal memory (r = -0.35, p ≤ 0.005), and visual memory (r = -0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003). In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment. These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.

Head-to-head comparison of four plasma neurofilament light chain (NfL) immunoassays

BackgroundNeurofilament Light Chain (NfL) is an emerging blood biomarker of neuro-axonal injury and neurodegeneration with the potential to be used in the clinical management of various neurological conditions. Various NfL immunoassays are in development on high-throughput automated systems, but little information is available related to the comparability between assays. In this study, we performed a head-to-head comparison of four NfL immunoassays using plasma samples from individuals with various neurological conditions. MethodsEDTA plasma samples in which NfL was ordered clinically were stratified according to diagnosis. NfL concentrations (pg/mL) in plasma were obtained using the Quanterix Simoa®, the Roche Elecsys, the Siemens Healthineers Atellica®IM, and the Fujirebio Lumipulse® NfL assays. Passing-Bablok regression analyses were performed to assess the correlation and bias between methods. Additionally, the distribution of NfL concentrations for each assay was assessed in three disease groups: amyotrophic lateral sclerosis (ALS) upon initial diagnosis, ALS treated, and multiple sclerosis (MS). ResultsThe R2 between assays were all ≥ 0.95, however, significant proportional bias was observed between some assays. In particular, the Roche Elecsys assay NfL concentrations were significantly lower (∼85 %) when compared against the other three assays. The four assays were comparable with regards to the percentage of patients that were identified as having an elevated NfL result in the various clinical groups: ALS initial diagnoses (83–94 %), ALS untreated (93–100 %), and MS (8–18 %). ConclusionsThis is the first study describing a head-to-head comparison of four automated NfL immunoassays. We demonstrate that there is a strong correlation between assays but a lack of standardization which is evident by the bias observed between some of the evaluated methods. These analytical differences will be important to consider when using NfL as a biomarker of neurodegeneration.

Serum neurofilament light chain as a prognostic marker of all-cause mortality in a national sample of US adults

Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20–85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60–2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.

Serum NfL and EGFR/NfL ratio mRNAs as biomarkers for phenotype and disease severity of myelin oligodendrocyte glycoprotein IgG-associated disease.

Myelin oligodendrocyte glycoprotein (MOG) IgG is frequently elevated in pediatric patients with acquired demyelinating syndrome (ADS). However, no specific biomarkers exist for phenotype classification, symptom severity, prognosis, and treatment guidance of MOG-IgG-associated disease (MOGAD). This study evaluated neurofilament light chain (NfL) and endothelial growth factor receptor (EGFR) mRNA expression levels in serum and cerebrospinal fluid (CSF) as potential biomarkers for MOGAD in Chinese children. This was a cross-sectional and single-center study. We enrolled 22 consecutive pediatric patients hospitalized with MOGAD and 20 control pediatric patients hospitalized for noninflammatory neurological diseases in Hebei Children's Hospital. Serum and CSF were collected from MOGAD patients within 3 days before immunotherapy. The mRNA levels of NfL and EGFR in serum and CSF were measured by real-time polymerase chain reaction (qPCR), and the EGFR/NfL ratio mRNA was calculated. These measurement values were then compared between disease groups and among MOGAD phenotypes. In addition, the correlations between the mRNAs of three markers (NfL, EGFR, EGFR/NfL ratio), extended disability status scale (EDSS) scores, and clinical phenotypes were analyzed. Serum and CSF NfL mRNA levels were significantly higher of acute-stage MOGAD patients than those of control patients (p< 0.05 and p< 0.01, respectively), while the mRNA levels of serum EGFR and EGFR/NfL ratio were significantly lower of MOGAD patients than those of controls (p < 0.05, p < 0.0001). Serum NfL mRNA was significantly correlated with mRNA of serum EGFR (r =0.480, p < 0.05). Serum and CSF NfL mRNA levels in MOGAD patients with the ADEM-like phenotype were also significantly higher than those in control patients (p < 0.01, p < 0.01) and optic neuritis (ON) phenotype (p < 0.05, p < 0.05). Both mRNAs of NfL in CSF and EGFR/NfL ratio in serum were correlated with EDSS scores (p < 0.05, r = 0.424; p < 0.05, r= -0.521). The mRNA levels of elevated NfL in serum and CSF as well as lower EGFR and EGFR/NfL ratio in serum could help distinguish acute-phase MOGAD. Higher mRNA levels of NfL in serum and CSF of MOGAD patients help distinguish ADEM-like phenotype. In addition, serum EGFR/NfL mRNA ratio is indicative ofdisease severity in pediatric patients with MOGAD. Further investigations arewarranted to elucidate the pathological mechanisms underlying these associations.