•Several options for automated high throughput assays are now readily available for neurofilament light chain.•The methods examined in this study are comparable when used clinically for diseases such ...as amyotrophic lateral sclerosis and multiple sclerosis.•There is a strong correlation between the assays evaluated, but a lack of standardization, evident by the biases observed.
Neurofilament 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.
EDTA 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).
The 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 %).
This 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.
•Critically illness polyneuropathy/myopathy (CIN/CIM) was more prevalent in COVID-19 ICU patients with severe illness.•Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) ...levels were higher in the CIN/CIM group and GFAp correlated with motor nerve amplitudes.•COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care.
The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).
An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.
111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.
CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.
COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.
This paper analyzes the effect of anthem protests on viewership for National Football League (NFL) games controlling for measures of NFL market-specific political beliefs and other demand ...determinants. To capture the effect of the protests on viewership, we create two classes of protests (unambiguous and ambiguous protests) and support the classification based on the meaning of the protest, actions by NFL owners, and statements by Donald Trump. Using data from all early and late-afternoon Sunday games from the 2014 through 2017 regular NFL seasons, we show that: (1) unambiguous protests reduce viewership in the week following the protests by about 15% while ambiguous protests do not generally produce statistically significant reductions in viewership; (2) the negative effect of unambiguous protests on viewership is particularly strong in metro locations that voted more heavily for Donald Trump in 2016; and (3) following Donald Trump's statements in week 3 of the 2017 season, both ambiguous and unambiguous protests increased and the increase in ambiguous protests was particularly large.
Background: Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity and has ...demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing disease progression remains unclear. Methods: We examined baseline and longitudinal blood NfL levels in 1421 persons with relapsing MS (RMS) and 596 persons with primary progressive MS (PPMS) from the pivotal ocrelizumab MS trials. NfL treatment-response and risk for disease worsening (including disability progression into the open-label extension period and slowly expanding lesions SELs on brain MRI) at baseline and following treatment with ocrelizumab were evaluated using time-to-event analysis and linear regression models. Findings: In persons from the RMS control arms without acute disease activity and in the entire PPMS control arm, higher baseline NfL was prognostic for greater whole brain and thalamic atrophy, greater volume expansion of SELs, and clinical progression. Ocrelizumab reduced NfL levels vs. controls in persons with RMS and those with PPMS, and abrogated the prognostic value of baseline NfL on disability progression. Following effective suppression of relapse activity by ocrelizumab, NfL levels at weeks 24 and 48 were significantly associated with long-term risk for disability progression, including up to 9 years of observation in RMS and PPMS. Interpretation: Highly elevated NfL from acute MS disease activity may mask a more subtle NfL abnormality that reflects underlying non-relapsing progressive biology. Ocrelizumab significantly reduced NfL levels, consistent with its effects on acute disease activity and disability progression. Persistently elevated NfL levels, observed in a subgroup of persons under ocrelizumab treatment, demonstrate potential clinical utility as a predictive biomarker of increased risk for clinical progression. Suppression of relapsing biology with high-efficacy immunotherapy provides a window into the relationship between NfL levels and future non-relapsing progression. Funding: F. Hoffmann-La Roche Ltd.
The overlapping symptoms of behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (such as depressive disorder, schizophrenia spectrum, and bipolar disorder) present a ...challenge for the differential diagnosis of bvFTD in middle and older-aged people. Neurofilaments are cytoskeletal proteins in the neurons, and several studies have reported elevated levels of neurofilament light chain (NfL) in cerebrospinal fluid of neurodegenerative as well as psychiatric disorders. The study aims to determine the utility of serum NfL levels as a biomarker to differentiate between bvFTD and psychiatric disorder. In our study, we investigated the levels of NfL in the serum of schizophrenia (n = 11), depression (n = 28), bipolar (n = 11), bvFTD (n = 20) patients and controls (n = 27) by single molecule array (Simoa) technology. The schizophrenia, depression and bipolar patients did not show significant changes in serum NfL levels in comparison to the control group (p > 0.99). The serum NfL levels were significantly elevated in bvFTD patients in comparison to the control cohort (p < 0.0001), depression (p < 0.0001), schizophrenia (p < 0.0002) and bipolar patients (p < 0.0083). We propose serum NfL as a biomarker to differentiate bvFTD from psychiatric disorders and to rule out neurodegeneration in the course of psychiatric disorders.
The primary hurdle to curing HIV is due to the establishment of a reservoir early in infection. In an effort to find new treatment strategies, we and others have focused on understanding the ...selection pressures exerted on the reservoir by studying how proviral sequences change over time.
To gain insights into the dynamics of the HIV reservoir we analyzed longitudinal near full-length sequences from 7 people living with HIV between 1 and 20 years following the initiation of antiretroviral treatment. We used this data to employ Bayesian mixed effects models to characterize the decay of the reservoir using single-phase and multiphasic decay models based on near full-length sequencing. In addition, we developed a machine-learning approach utilizing logistic regression to identify elements within the HIV genome most associated with proviral decay and persistence. By systematically analyzing proviruses that are deleted for a specific element, we gain insights into their role in reservoir contraction and expansion.
Our analyses indicate that biphasic decay models of intact reservoir dynamics were better than single-phase models with a stronger statistical fit. Based on the biphasic decay pattern of the intact reservoir, we estimated the half-lives of the first and second phases of decay to be 18.2 (17.3 to 19.2, 95%CI) and 433 (227 to 6400, 95%CI) months, respectively.In contrast, the dynamics of defective proviruses differed favoring neither model definitively, with an estimated half-life of 87.3 (78.1 to 98.8, 95% CI) months during the first phase of the biphasic model. Machine-learning analysis of HIV genomes at the nucleotide level revealed that the presence of the splice donor site D1 was the principal genomic element associated with contraction. This role of D1 was then validated in an
system. Using the same approach, we additionally found supporting evidence that HIV
may confer a protective advantage for latently infected T cells while
was associated with clonal expansion.
The nature of intact reservoir decay suggests that the long-lived HIV reservoir contains at least 2 distinct compartments. The first compartment decays faster than the second compartment. Our machine-learning analysis of HIV proviral sequences reveals specific genomic elements are associated with contraction while others are associated with persistence and expansion. Together, these opposing forces shape the reservoir over time.
Schematic illustration of the synthesis of porous polymeric film with GMA functionality. 1) Bare gold surface, 2) Self-assembling of MAC monolayer, 3) Synthesis of GMA based porous polymeric film, 4) ...Removal of PVA.
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•Constructing of generic bioinspired analytical tools.•Novel biosensors for diagnosis of Parkinson's disease.•Synthesis of polymerizable amino acid derivatives.•Porous polymeric film with glycidyl methacrylate (GMA) functionality.
Neurofilament light chain (NfL) has been classified as one of the most prominent biomarkers for identification of Parkinson's disease that is manifested by loss of dopaminergic neurons in the gray matter of the brain with the formation of cytoplasmic inclusion bodies in the brain tissue. Novel biosensors are needed for diagnosis of Parkinson's disease as well as monitoring of the treatment process. So, the concentration of NfL in cerebrospinal fluid has been reported to be useful in distinguishing Parkinson's disease from atypical Parkinson's syndromes. For this purpose, an electrochemical immunoaffinity biosensor having limit of detection (LOD), and limit of quantitation (LOQ) as 5.21 ng/L and 15.79 ng/L has been developed for the determination of NfL concentration. In this study, glycidyl methacrylate (GMA) functional monomer was used to form thin polymeric films on the electrode surface and the anti-NfL antibody was immobilized via covalent linkage with GMA as a biorecognition agent.
•Well-supported cognitively unimpaired plasma NfL reference intervals were determined.•Observed 97.5th percentile NfL concentrations increased at a rate of 3.1% per year of age.•Decade-wide reference ...intervals will aid in the evaluation of potential neurodegeneration.
Neurofilament light chain (NfL) is an emerging biomarker of neurodegenerative disease progression. As plasma NfL increases with age, characterization of NfL concentrations in an age-stratified cognitively unimpaired population was assessed.
EDTA-plasma samples were measured using the Simoa® NF-light™ Advantage Kit assay. One-sided reference intervals were established from 1100 cognitive normal individuals (588 male, 512 female) aged 20 to 95 years. Of those, 927 samples were obtained from the Mayo Clinic Study of Aging cohort (age > 50 years), and the remainder (age < 50 years) were obtained from individuals without known neurological conditions. All samples were from individuals without known chronic kidney disease, stroke or myocardial infarction, and a body mass index < 30 kg/m2.
The 97.5th percentile limits for the following age ranges (in years) were (pg/mL): 20 s: ≤8.4, 30 s: ≤11.4, 40 s: ≤15.4, 50 s: ≤20.8, 60 s: ≤28.0, 70 s: ≤37.9, 80+: ≤51.2. Sex had no significant effect on reference intervals. Observed NfL concentrations increased at a rate of 3.1 % per year of age.
Characterization of the rate of NfL concentration increase and decade-wide reference intervals from a neurologically well-characterized patient population will aid in interpretation of NfL during the clinical evaluation of a potential neurodegenerative disease.
Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons.
To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases.
Study ...included 37 healthy dogs, 31 dogs with idiopathic epilepsy (IE), 45 dogs with meningoencephalitis of unknown etiology (MUE), 20 dogs with hydrocephalus, and 19 dogs with brain tumors.
Cohort study. Serum NfL concentrations were measured in all dogs using single-molecule array technology.
Serum NfL concentration in dogs with each structural disease was significantly higher than in healthy dogs and dogs with IE (P = .01). The area under the receiver operating characteristic curve of NfL for differentiating between dogs with structural diseases and IE was 0.868. An optimal cutoff value of the NfL 27.10 pg/mL had a sensitivity of 86.67% and a specificity of 74.19% to differentiate the dogs with IE from those with structural brain diseases. There were significant correlations between NfL concentrations and lesion size: (1) MUE, P = .01, r = 0.429; (2) hydrocephalus, P = .01, r = 0.563.
Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus.
Background
This retrospective follow‐up study aims to investigate the dynamic longitudinal change of plasma neurofilament light (NfL) levels after antiretroviral therapy (ART) initiation in a cohort ...of people living with human immunodeficiency virus (HIV) (PWH).
Methods
We tested a convenience sample of 116 patients from the NORTHIV study. Plasma NfL levels—measured using Single molecule array (Simoa) technology—as well as other laboratory parameters were collected at baseline, weeks 4, 48, 96, and 144. Linear mixed‐effects models were estimated to evaluate longitudinal change over time. Baseline CD4+ T‐cell levels, CDC classification, and HIV RNA levels were considered. Models were adjusted by age, sex, treatment regimen, and baseline serum creatinine levels.
Results
Plasma NfL levels were higher at baseline and also declined faster during the follow‐up for participants with CD4+ count <100 cells/µl compared with >100 cells/µl. No significant difference was found between the CD4+ strata 100–199 and 200–499/µl. Participants with CDC classification stages B and C had higher levels of plasma NfL at baseline, as well as faster decline compared with participants with stage A. No significant main effects or change over time was found in baseline HIV RNA levels, treatment regimen, or sex.
Conclusion
Plasma NfL is a sensitive biomarker to assess ongoing central nervous system injury in PWH. Plasma NfL concentrations decline relatively fast following ART initiation and then stabilize after 48 weeks. Plasma NfL concentrations are associated with CD4+ count and stage of HIV disease. No correlations were seen with different ART regimens.
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