Neurofilament Light Chain Research Articles

Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study

BackgroundConcussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion. MethodsSerum samples from 86 PPCS individuals aged 18–30 years, 2–6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison. ResultsNo significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25–40% lower than in healthy individuals (p ≤ 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites. ConclusionNFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.

Synaptic vesicle glycoprotein 2 A in serum is an ideal biomarker for early diagnosis of Alzheimer’s disease

BackgroundPrevious studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer’s disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD.MethodsIn this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed.ResultsBoth CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD.ConclusionsSerum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.

Plasma biomarkers for predicting the development of dementia in a community-dwelling older Japanese population.

To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population. A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years. Plasma biomarkers were quantified using a Simoa HD-X analyzer. A Cox proportional hazards model was used to estimate the hazard ratios of each plasma biomarker level for the risk of dementia. During the follow-up, 151 participants developed dementia, of whom 108 had Alzheimer disease (AD) and 43 non-Alzheimer dementia (non-AD). Lower plasma Aβ42/40 levels and higher plasma p-τ181 levels were significantly associated with developing AD but not non-AD, whereas significant associations were observed between higher plasma levels of GFAP and NfL and risk of both AD and non-AD (all P for trend <0.05). In addition, adding these four plasma biomarkers into a model consisting of the total score of the dementia risk model significantly improved the predictive ability for incident dementia. Our findings suggest that plasma Aβ42/40 and p-τ181 are specific markers of AD, and plasma GFAP and NfL are potential biomarkers for all-cause dementia in the general Japanese older population. In addition, the measurement of these plasma biomarkers may be a useful and relatively low-invasive procedure for identifying individuals at high risk for developing dementia in clinical practice.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

Racial discrimination during middle age predicts higher serum phosphorylated tau and neurofilament light chain levels a decade later: A study of aging black Americans.

Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans. The present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). We hypothesized that racial discrimination assessed during middle age would predict increases in these serum biomarkers as the participants aged into their 60s. Our findings indicate that exposure to various forms of racial discrimination during a person's 40s and early 50s predicts an 11-year increase in both serum p-tau181 and NfL. Racial discrimination was not associated with subsequent levels of GFAP. These findings suggest that racial discrimination in midlife may contribute to increased AD pathology and neurodegeneration later in life. A 17-year longitudinal study of Black Americans. Assessments of change in serum p-tau181, neurofilament light, and glial fibrillary acidic protein. Exposure to racial discrimination during middle age predicted increases in p-tau181 and neurofilament light. Education was positively related to both p-tau181 and exposure to racial discrimination.

Effect of Modified Mediterranean Diet on Serum Neurofilament Light Chain: Analysis from a Randomized Clinical Trial (P2-6.004)

Effect of Modified Mediterranean Diet on Serum Neurofilament Light Chain: Analysis from a Randomized Clinical Trial (P2-6.004)

Serum Neurofilament Light Chain (sNfL) as Potential Biomarker for Immune Check Point Inhibitor (ICI) Mediated Limbic Encephalitis – A Case Series (P6-5.025)

Serum Neurofilament Light Chain (sNfL) as Potential Biomarker for Immune Check Point Inhibitor (ICI) Mediated Limbic Encephalitis – A Case Series (P6-5.025)

Neurofilament Light Chain in Spinal Bulbar Muscle Atrophy and Amyotrophic Lateral Sclerosis 4 (P2-11.010)

Neurofilament Light Chain in Spinal Bulbar Muscle Atrophy and Amyotrophic Lateral Sclerosis 4 (P2-11.010)

Evaluation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels During Eculizumab and Ravulizumab Treatments in Aquaporin-4-Positive (AQP4+) Neuromyelitis Optica Spectrum Disorder (NMOSD) (S32.004)

Evaluation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels During Eculizumab and Ravulizumab Treatments in Aquaporin-4-Positive (AQP4+) Neuromyelitis Optica Spectrum Disorder (NMOSD) (S32.004)

Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy (P5-3.001)

Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy (P5-3.001)

Neurofilament Light Chain (NfL) Levels are Increased After Sleep in Parkinson Disease (PD) (P7-3.002)

Neurofilament Light Chain (NfL) Levels are Increased After Sleep in Parkinson Disease (PD) (P7-3.002)

Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia.

Plasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer's Disease (AD). Here, we investigated plasma Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NfL) and Phosphorylated-tau-181 (pTau 181) in AD and in its early stages: Subjective cognitive decline (SCD) and Mild cognitive impairment (MCI). This study included 152 patients (42 SCD, 74 MCI and 36 AD). All patients underwent comprehensive clinical and neurological assessment. Blood samples were collected for Apolipoprotein E (APOE) genotyping and plasma biomarker (GFAP, NfL, and pTau 181) measurements. Forty-three patients (7 SCD, 27 MCI, and 9 AD) underwent a follow-up (FU) visit after 2 years, and a second plasma sample was collected. Plasma biomarker levels were detected using the Simoa SR-X technology (Quanterix Corp.). Statistical analysis was performed using SPSS software version 28 (IBM SPSS Statistics). Statistical significance was set at p < 0.05. GFAP, NfL and pTau 181 levels in plasma were lower in SCD and MCI than in AD patients. In particular, plasma GFAP levels were statistically significant different between SCD and AD (p=0.003), and between MCI and AD (p=0.032). Plasma NfL was different in SCD vs MCI (p=0.026), SCD vs AD (p<0.001), SCD vs AD FU (p<0.001), SCD FU vs AD (p=0.033), SCD FU vs AD FU (p=0.011), MCI vs AD (p=0.002), MCI FU vs AD (p=0.003), MCI FU vs AD FU (p=0.003) and MCI vs AD FU (p=0.003). Plasma pTau 181 concentration was significantly different between SCD and AD (p=0.001), MCI and AD (p=0.026), MCI FU and AD (p=0.020). In APOE ϵ4 carriers, a statistically significant increase in plasma NfL (p<0.001) and pTau 181 levels was found (p=0.014). Moreover, an association emerged between age at disease onset and plasma GFAP (p = 0.021) and pTau181 (p < 0.001) levels. Plasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia.

Cognitive Impairment in Long COVID: Molecular Mimicry and Neurofilament Light Chain (NfL) as Disease Mechanisms (P11-13.001)

Cognitive Impairment in Long COVID: Molecular Mimicry and Neurofilament Light Chain (NfL) as Disease Mechanisms (P11-13.001)

Cerebrospinal Fluid and Plasma Immune Cell Phenotyping Combined with Neurofilament Light Chain as Biomarkers of Inflammatory Activity and Disease Modifying Therapy Responsiveness in Multiple Sclerosis (S42.009)

Cerebrospinal Fluid and Plasma Immune Cell Phenotyping Combined with Neurofilament Light Chain as Biomarkers of Inflammatory Activity and Disease Modifying Therapy Responsiveness in Multiple Sclerosis (S42.009)

Prognostic Value of Serum Neurofilament Light Chain for Disease Activity in Patients with Relapsing Multiple Sclerosis: Results from Subgroup Analysis Based on Body Mass Index and Age from the Phase 3 ASCLEPIOS I/II Trials (P6-6.011)

Prognostic Value of Serum Neurofilament Light Chain for Disease Activity in Patients with Relapsing Multiple Sclerosis: Results from Subgroup Analysis Based on Body Mass Index and Age from the Phase 3 ASCLEPIOS I/II Trials (P6-6.011)

Baseline Serum Neurofilament Light Chain Levels Predict Future Disease Activity Irrespective of Race/Ethnicity: Results from the Phase 3 ASCLEPIOS I/II Trials (P9-6.006)

Baseline Serum Neurofilament Light Chain Levels Predict Future Disease Activity Irrespective of Race/Ethnicity: Results from the Phase 3 ASCLEPIOS I/II Trials (P9-6.006)

Serum Neurofilament Light Chain Levels are Elevated in Stiff Person Syndrome Spectrum Disorders (P1-14.008)

Serum Neurofilament Light Chain Levels are Elevated in Stiff Person Syndrome Spectrum Disorders (P1-14.008)

Prognostic Value of On-treatment Serum Neurofilament Light Chain for New or Enlarging T2 Lesions in People with Relapsing Multiple Sclerosis: Pooled Analysis of the ASCLEPIOS I/II Trials (S42.003)

Prognostic Value of On-treatment Serum Neurofilament Light Chain for New or Enlarging T2 Lesions in People with Relapsing Multiple Sclerosis: Pooled Analysis of the ASCLEPIOS I/II Trials (S42.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Ofatumumab Reduces Clinical and Radiological Activity in People with Recently Diagnosed Treatment-naive Relapsing Multiple Sclerosis Irrespective of Baseline Serum Neurofilament Light Chain Levels (P9-6.008)

Ofatumumab Reduces Clinical and Radiological Activity in People with Recently Diagnosed Treatment-naive Relapsing Multiple Sclerosis Irrespective of Baseline Serum Neurofilament Light Chain Levels (P9-6.008)