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A frame analysis was conducted of recent coverage by sports journalists of the on-again off-again possibility that Colin Kaepernick might sign a contract to play with a team in the National Football League (NFL). Kaepernick was blacklisted by league and team officials angry at, and hoping to avert public backlash from, Kaepernick's 2016 decision to kneel during the national anthem to protest systemic police brutality and mass incarceration. The analysis enabled the creation of champions, distractions, exile, futility, impact, and spectacle frames. The analysis affirms that journalists may be priming readers to conclude that the NFL has learned its lesson, that some officials should be congratulated for generating the bravery to welcome Kaepernick back to the league and commended for their newfound insights about racism. The episodic frames emerging from coverage of the tryouts and a possible signing affirm that the "new appreciation" of Kaepernick has become a nonthreatening reverence for his place in history. Kaepernick's exile now reads like a one-off, an outlier, rather than a glaring example of the systemic racism that still infects the league. Frames affirm that the NFL—with help from the nation's sports writers and commentators—has taken control of the narrative with which fans process an athlete's activism. They have legitimized the narrow space provided by the league for player protest. [ABSTRACT FROM AUTHOR]

Background: Orthopaedic surgeons play a critical role in ensuring the health and safety of professional athletes. Despite the privilege of treating elite athletes, there exists great financial exposure to individual physicians in the event of a malpractice lawsuit. Hypothesis/Purpose: The purpose of this study was to evaluate and model malpractice liability exposure of the sports medicine surgeon caring for athletes in the National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) with respect to player position and additional supplemental malpractice insurance needs. It was hypothesized that routine liability coverage cannot adequately address the demands of caring for elite athletes in professional sports leagues. Study Design: Economic and Decision Analysis; Level of evidence, 3. Methods: In total, 2447 NFL, 992 MLB, and 980 NHL player contracts from the 2022-2023 season were aggregated from a publicly available online database. Position, team, total contract value, and mean yearly salary were noted. Risk ratios were calculated with respect to 1 million US dollars (USD) and 3 million USD of annual occurrence-based malpractice liability awards and used to generate a "covered-to-treat" analysis. Supplemental malpractice liability insurance was quantified. Results: Assuming 1 million and 3 million USD occurrence-based awards covered by malpractice liability insurance, team physicians can fully treat 17.3% and 50.0% of NFL players, 43.2% and 59.7% of MLB players, and 13.6% and 41.0% of NHL players, without incurring additional personal financial risk, from a risk-based medicolegal model. Liability policies of 52.6 million, 108.1 million, and 64.1 million USD are required to treat 95% of NFL, MLB, and NHL players, respectively. Positions carrying the greatest risk ratios are quarterback (QB) (9.9) in the NFL, right field (15.1) in the MLB, and center (5.7) in the NHL. Conclusion: Sports medicine specialists caring for elite athletes face potential personal financial risk due to insufficient medicolegal coverage. While coverage may vary among different practice settings including private, academic, or public state institutions, medical malpractice risk is crucial in partnerships between sports franchises, hospitals, players, agents, and physicians to protect sports medicine physicians and offer the highest-quality care. [ABSTRACT FROM AUTHOR]

Background and aim: COVID-19 is associated with neurological complications, termed neuro-COVID, affecting patient outcomes. We aimed to evaluate the association between serum neurofilament light chain (NfL) and S100B biomarkers with the presence of neurological manifestations and functional prognosis in COVID-19 patients. Methods: A multicenter prospective cohort study was conducted in three hospitals in the Emilia-Romagna region, Italy, from March 2020 to April 2022. Hospitalized patients with PCR-confirmed COVID-19 were enrolled. Serum S100B and NfL levels were measured in the acute or subacute phase after admission. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analyses. Statistical analyses were performed to evaluate the association between biomarkers, clinical/laboratory variables, and prognosis, specifically focusing on worsening of the modified Rankin Scale (mRS) from admission to discharge. Results: A total of 279 patients (153 males, median age 76.7 years) were included. Among them, 69 (24.7%) developed neuro-COVID. Serum NfL levels were significantly higher in the neuro-COVID group (median 110 vs 68.3; p = 0.035) and correlated with severe encephalopathy and extracranial neurologic manifestations. The ROC analysis showed low accuracy in the discrimination between the two groups for both NfL and S100B. Key predictors of worsening mRS included mechanical ventilation (OR = 9.56, 95% CI = 1.67–54.75; p = 0.011), severe encephalopathy (OR = 5.10, 95% CI = 1.58–16.19; p = 0.006), and elevated S100B levels (OR = 2.62, 95% CI = 1.10–6.46; p = 0.037). Conclusions: Serum NfL and S100B biomarkers were not accurate in discriminating neuro-COVID patients, however NfL levels were associated with severe and extracranial neuro-COVID, while S100B with functional outcomes, potentially informing clinical management. [ABSTRACT FROM AUTHOR]

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial. Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser. PwMS were evaluated for highly active profiles by applying the aggressive disease course criteria proposed by ECTRIMS. Serum/CSF values were logarithmically transformed and compared across groups using one-way ANOVA, while correlations were calculated using Pearson's correlations. ROC analysis and AUC comparisons for diagnostic performance of the three biomarkers were computed in an explorative analysis. Results: Serum BDNF (sBDNF) concentrations were higher in treatment naïve pwMS with disease onset after the age of 40 years (p = 0.029), in pwMS with ≥2 gadolinium-enhancing lesions (p = 0.009) and with motor, cerebellar, cognitive or sphincter symptoms at onset (p = 0.036). BDNF correlated positively with NfL (r = 0.198, p = 0.014) and GFAP (r = 0.253, p = 0.002) in serum, but not in CSF. Neurological patients with an acute inflammatory relapse showed significantly higher sBDNF levels (p = 0.03) compared to somatoform controls, while patients without acute relapse did not differ from somatoform controls (p = 0.4). Better diagnostic performance was found for sBDNF than sNfL and sGFAP in differentiating between patients with vs. without 2 or more gadolinium-enhancing lesions (p < 0.05) and for sBDNF as compared to sNfL for separating patients with disease onset after vs. before age of 40 years. Conclusion: In pwMS, BDNF serum levels differ depending on disease-related characteristics, suggesting that not only inflammatory activity but also remyelination capacities may vary with disease severity. BDNF is increased when other biomarkers of neuroaxonal damage and neurodegeneration, such as NfL and GFAP, are elevated, possibly as a compensatory mechanism, and reflect possibly further pathophysiological aspects in MS beyond NfL and GFAP, probably including an apoptotic role for BDNF in neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Charcot–Marie–Tooth disease (CMT), a slowly advancing hereditary nerve disorder, presents a significant challenge in the medical field. Effective drugs for treatment are lacking, and we struggle to find sensitive markers to track the disease's severity and progression. In this study, our objective was to investigate the levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) in individuals with CMT and to compare them to a control group. Our primary goal is to determine whether these biomarker levels are related to the severity of the disease. Methods: Initially, 44 patients with CMT and 44 controls participated in this study. CMT diagnosis was approved by genetic testing. Disease severity was assessed through clinical evaluations using the CMT Neuropathy Score version 2 (CMTNSv2). NfL and GFAP concentrations were measured using Single molecule array, while FGF-21 and GDF-15 concentrations were measured by enzyme-linked immunosorbent assays. Results: In the group of patients with CMT, the concentrations of GDF15, FGF21, NfL, and GFAP were significantly higher than in the control group (p < 0.05). NfL and GFAP levels were correlated with the CMTNSv2 score (rs = 0.46, p = 0.002; rs = 0.31, p = 0.04). Conclusion: Our study has provided confirmation that plasma concentrations of NfL, GFAP, GDF15, and FGF21 are significantly elevated in patients with CMT compared to controls. Furthermore, NfL and GFAP levels were correlated with the clinical severity of CMT. These findings suggest that NfL and GFAP can be reliable disease indicators in future research. [ABSTRACT FROM AUTHOR]

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels. [ABSTRACT FROM AUTHOR]

The G4C2 hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. The model displays key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis. However, the AAV-(G4C2)66 mouse model in this study has marginal neurodegeneration with negligible neuronal loss, or clinical deficits. Human C9orf72 is typically associated with altered TAR DNA-binding protein (TDP-43) function, yet studies of this rodent model revealed no significant evidence of TDP-43 dysfunction. While our findings indicate and support that this is a highly valuable robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease- associated TDP-43 dysfunction or clinical impairment. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS. [ABSTRACT FROM AUTHOR]

Guided by the Symbiotic Sustainability Model, this study examines how partnership characteristics influence people’s evaluation of corporate-nonprofit alliances and how attitude toward partner organizations and partnerships influence intention to support the corporation. Using the NFL’s partnership with a LGBTQ+ sports organization as a context, this study analyzed data from 459 participants. Findings show that using the nonprofit partner as the communication source enhances the NFL’s reputation, but, this effect disappears after controlling for other factors. Partnership type indirectly impacts the NFL support intention, mediated by foundation attitude. Attitudes toward the NFL, the nonprofit, and the partnership, are all related to the willingness to support the NFL. This study offers implications for strategic communication to enhance reputation and public support. [ABSTRACT FROM AUTHOR]

Introducing a special issue looking at football coaches, this essay challenges readers to think about the immense power and privileges afforded by white male coaches alongside their refusal to leverage their immense platforms to advance justice within and beyond the coaching ranks. Focusing on the politics of football coaches and the entrenched place of white men on the sidelines, this special issue seeks to demonstrate the power and importance of football coaches as a measuring stick of race, gender, sexuality, politics, and so much more. To understand the history of football coaches is to understand America, its persistent color lines, reactionary politics, and everything from the media to the 2024 election. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by relentless and progressive loss of motor neurons. A molecular diagnosis, supported by the identification of specific biomarkers, might promote the definition of multiple biological subtypes of ALS, improving patient stratification and providing prognostic information. Here, we investigated the levels of neurofilament light chain (NfL), chitotriosidase (CHIT1) and microRNA-181b (miR-181b) in the cerebrospinal fluid (CSF) of ALS subjects (N = 210) as well as neurologically healthy and neurological disease controls (N = 218, including N = 74 with other neurodegenerative diseases) from a large European multicentric cohort, evaluating their specific or combined utility as diagnostic and prognostic biomarkers. NfL, CHIT1 and miR-181b all showed significantly higher levels in ALS subjects compared to controls, with NfL showing the most effective diagnostic performance. Importantly, all three biomarkers were increased compared to neurodegenerative disease controls and, specifically, to patients with Alzheimer's disease (AD; N = 44), with NfL and CHIT1 being also higher in ALS than in alpha-synucleinopathies (N = 22). Notably, ALS patients displayed increased CHIT1 levels despite having, compared to controls, a higher prevalence of a polymorphism lowering CHIT1 expression. While no relationship was found between CSF miR-181b and clinical measures in ALS (disease duration, functional disability, and disease progression rate), CSF NfL was the best independent predictor of disease progression and survival. This study deepens our knowledge of ALS biomarkers, highlighting the relative specificity of CHIT1 for ALS among neurodegenerative diseases and appraising the potential diagnostic utility of CSF miR-181b. [ABSTRACT FROM AUTHOR]

A manager's prior experience may affect an organization's resource allocation decisions and its performance. I examine this issue in the context of National Football League (NFL) franchises. I find that teams with coaches from an offensive background spend 5.5% points more of their salary cap space on offensive personnel, while a defensive background does not significantly affect the share of resources allocated to defensive personnel. While additional salary resources committed to offensive and defensive personnel do improve team performance in those respective areas, marginal improvements in offensive and defensive performance associated with greater spending are generally unaffected by the coach's background, a finding suggesting that a coach's background does not confer an informational advantage on certain types of personnel. I further find no evidence of significant differences in the effects that spending on offence and defence respectively have on team performance, suggesting efficiency within this labour market. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The A/T/N (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimers disease (AD) diagnosis and can encompass additional changes such as inflammation (I). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. HIGHLIGHTS: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate.

While sports fandom and social media advertising have been widely studied, and all major, professional teams use social media campaigns for direct sales, there is surprisingly little research on the relationship between fans' social media engagement behavior (SMEB) and their purchase intention (PI), and none that differentiates PI across different platforms and sports contexts. This study addresses those gaps by exploring (a) how different kinds of fans engage their teams' advertising on various social media and (b) how those different behaviors predict PI in different contexts. To do so, we utilized an SMEB framework to interpret survey data (N = 452) of U.S. sports fans' social media engagement with their favorite teams over six popular platforms for two situations—in-game and out-of-game. Regression analyses determined the extent to which those behaviors predict PI across different sports and platforms during and outside of games. Our results show that fan SMEB varies by sport, platform, and situation. Furthermore, we found that information-acquiring social media behaviors—such as checking scores—best predict PI in-game, while fan-identity cultivation social media behaviors—such as posting—best predict PI out-of-game. In addition, PI predictability varies across platform and game situation, but not across age, gender, or even level of fandom. By contextualizing the relationship between fan SMEB and PI, our study lays a foundation to address these lingering gaps in the sport communication literature while providing actionable insights for teams and brands seeking more effective sales campaigns across an array of social media. [ABSTRACT FROM AUTHOR]

Abstract Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer’s disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65–75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

Background and purpose Methods Results Discussion The purpose was to explore the prognostic utility of neurofilament light chain (NfL) in patients with immune‐mediated polyradiculoneuropathies (IMPs).This retrospective monocentric study analysed serum and cerebrospinal fluid samples from patients diagnosed with IMP collected prior to treatment initiation. NfL concentrations were correlated with clinical outcomes, including F score and hospitalization duration.Amongst 115 IMP patients tested, baseline cerebrospinal fluid and serum NfL (sNfL) concentrations were higher in acute inflammatory axonal polyradiculoneuropathy (AIAP) than other IMP variants. In the AIAP cohort, a positive correlation was observed between baseline sNfL concentrations, F score and hospitalization duration. Multivariate linear regression analysis further supported the predictive relationship between elevated baseline sNfL concentrations and clinical outcomes. Using receiver operating characteristic analysis, a cut‐off value for sNfL of 351 pg/mL was found to predict an F score >3 in AIAP with a sensitivity of 40% and specificity of 81.8%. AIAP patients with sNfL concentrations above this threshold required longer hospitalization (extended by 15 days).Our findings highlight the potential of baseline sNfL as an effective marker for distinguishing between IMP variants and predicting the prognosis of AIAP. Further validation may facilitate translation of sNfL into clinical practice, potentially identifying high‐risk patients for tailored treatment approaches. [ABSTRACT FROM AUTHOR]

Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model. [ABSTRACT FROM AUTHOR]

The National Football League (NFL) sets its regular season schedule to optimize viewership andminimize competitive inequities.One inequity assumed to impact team performance is rest differential, defined as the relative number of days between games. Using Bayesian state space models on both game outcomes and betting market data, we estimate the competitive effect of rest differential in American football. We find that the most commonly referred to inequities--both the bye week rest advantage and the mini-bye week rest advantage--currently show no significant evidence of providing the rested team a competitive edge. Further, we trace a decline in the advantage of a bye week to a 2011 change to the NFL's Collective Bargaining Agreement, which represents a natural experiment to test the relevance of rest and preparation in football. Prior to the agreement, NFL teams off a bye week received a significant advantage (+2.2 points per game), but since 2011, that benefit has been mitigated. Our findings imply that extra days with practice time, and not extra days off alone, are the primary driver of any NFL rest advantage. [ABSTRACT FROM AUTHOR]

We analyse changes in the National Football League (NFL) due to ghost games in 2020. The home bias disappears as expected. This also applies to semi-ghost games with significantly fewer spectators than regular games and to referee decisions regarding penalties. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Plasma phosphorylated tau‐217 (p‐tau217) and neurofilament light (NfL) can differentiate between different dementias in selected cohorts. We aim to test the discrimination potential of these markers in a real‐world cohort. METHODS: We measured p‐tau217 (ALZpath) and NfL (Quanterix) in 415 (unselected) consecutive memory clinic patients. Biomarker levels were dichotomized as low/high to create four biomarker profiles based on p‐tau217 and NfL levels. RESULTS: p‐Tau217 levels were highest in patients with Alzheimer's disease (AD) dementia, whereas NfL levels were highest in patients with frontotemporal dementia (FTD). Low p‐tau217/low NfL was associated mostly with non‐neurological diagnoses (79%), and high p‐tau217/low NfL indicated AD pathology at any stage (84%). Low p‐tau217/high NfL indicated FTD (38%) and high p‐tau217/high NfL indicated AD dementia (87%). DISCUSSION: p‐Tau217 can identify AD pathology at any disease stage. NfL can differentiate FTD from other diagnoses (e.g., AD dementia). Plasma p‐tau217 and NfL can support clinical decision‐making, and we suggest using them as complements to standard clinical assessment. Highlights: Phosphorylated tau‐2017 (p‐tau217) can detect Alzheimer's disease (AD) across the clinical continuum.Neurofilament light (NfL) can differentiate frontotemporal dementia (FTD) from other diagnoses (AD dementia, dementia with Lewy bodies [DLB], and Psychiatry).p‐Tau217 may detect AD co‐pathology in other diseases or dementia types (e.g., DLB).p‐Tau217 and NfL show potential for clinical implementation. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer’s disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65–75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging. [ABSTRACT FROM AUTHOR]

Inflammation of the brain is called encephalitis and may result in acute and chronic brain damage. Encephalitis can be caused by various pathogens, especially neurotropic viruses, or can occur in the context of autoimmune diseases. Encephalitis is often difficult to diagnose and to monitor precisely during the course of the disease. Thanks to highly specific detection technology, components of the neuron skeleton, such as neurofilaments, can now be reliably quantified in the peripheral blood besides cerebrospinal fluid (CSF). Among them, neurofilament light chain (NfL) has demonstrated wide utility due to high preanalytical stability, robust diagnostic technology, and excellent reproducibility. We provide an overview of how NfL has advanced diagnostics in encephalitis and outline future avenues in research needs and possible clinical applicability of NfL in adults and children. [ABSTRACT FROM AUTHOR]

Background: Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS). Objectives: This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers. Methods: RIS individuals were included retrospectively and compared with HC. ChPs were automatically segmented using an in-house automated algorithm and manually corrected. Results: A total of 124 patients fulfilled the 2023 RIS criteria, and 55 HCs were included. We confirmed that ChPs are enlarged in RIS versus HC (mean (±SD) normalized ChP volume: 17.24 (±4.95) and 11.61 (±3.58), respectively, p < 0.001). Larger ChPs were associated with more periventricular lesions (ρ = 0.26; r 2 = 0.27; p = 0.005 for the correlation with lesion volume, and ρ = 0.2; r 2 = 0.21; p = 0.002 for the correlation with lesion number) and lower thalamic volume (ρ = −0.38; r 2 = 0.44; p < 0.001), but not with lesions in other brain regions. Conversely, ChP volume did not correlate with biological markers. No significant difference in ChP volume was observed between subjects who presented or did not have a clinical event or between those with or without imaging disease activity. Conclusions: This study provides evidence that ChP volume is higher in RIS and is associated with measures reflecting periventricular pathology but does not correlate with biological, radiological, or clinical markers of disease activity. [ABSTRACT FROM AUTHOR]

Objective: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Method s : In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail‐arm, flail‐leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival. Results: Mean sNfL was ‐ compared to typMN (75.7 pg/mL, n = 1791) ‐ significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail‐arm (46.4 pg/mL, n = 283), flail‐leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001). Conclusions: This study underscored the correlation of ALS phenotypes – differentiated for motor neuron involvement and region of onset/propagation – with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Hamstring strain injuries (HSIs) are prevalent in US National Football League (NFL) players, but there is a paucity of information regarding imaging characteristics, injury severity, and player factors associated with time missed and risk of recurrent injury. Purpose: To describe player, football activity, clinical, and imaging characteristics of NFL players with HSIs, as well as determine player characteristics, clinical examination results, and magnetic resonance imaging (MRI) findings associated with injury occurrence, severity, and missed time. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A retrospective cohort of NFL players with acute HSI (n = 180) during the 2018-2019 season was identified. Injury data were collected prospectively through a league-wide electronic health record system. Three musculoskeletal radiologists graded MRI muscle injury parameters using the British Athletics Muscle Injury Classification (BAMIC) system. Player, football, clinical, and imaging characteristics were correlated with HSI incidence and severity and with missed time from sport. Results: Of the 1098 HSIs identified during the 2018-2019 season, 416 (37.9%) were randomly sampled, and 180 (43.3%) had diagnostic imaging available. Game activity, preseason period, and wide receiver and defensive secondary positions disproportionately contributed to HSI. The biceps femoris was the most commonly injured muscle (n = 132, 73.3%), followed by the semimembranosus (n = 24, 13.3%) and semitendinosus (n = 17, 9.4%) muscles. The most common injury site was the distal third of the biceps femoris and semitendinosus muscles (n = 60, 45.5% and n = 10, 58.8%, respectively) and central part of the semimembranosus muscle (n = 17, 70.8%). Nearly half of the injuries (n = 83, 46.1%) were BAMIC grade 2; 25.6% (n = 46), grade 3; and 17.8% (n = 32), grade 4. MRI showed sciatic nerve abnormality in 30.6% (n = 55) of all HSIs and 81.3% (n = 26) of complete tendon injuries. BAMIC grade correlated with both median days and games missed. Combined biceps femoris and semitendinosus injuries resulted in the highest median days missed (27 days). Conclusion: Among NFL players with acute HSIs, the most common injury was a moderate-severity injury of the distal biceps femoris. BAMIC grade was associated with missed time. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX), a drug utilized in cancer and rheumatoid arthritis treatment, is associated with acute and chronic neurodegenerative alterations. Spirulina platensis (SP) has several important phytochemical substances that act as free radical scavengers or natural antioxidants. The current study investigated the possible effects of the blue-green alga Spirulina platensis on cerebellar damage in male rats exposed to methotrexate. Forty (40) adult male albino rats were randomly divided into 4 groups (n = 10) and treated for one week: GI, the control group; GII was orally given 1000 mg SP/kg/daily, GIII was given a single intraperitoneal injection of MTX 75 mg/kg at the first day, and continued under the normal condition without other treatment till the end of the experiment, and GIV received both SP and MTX together with the same previous doses and duration. Neurobehavioral, histopathological, histochemical, immunohistochemical, ultrastructural, molecular, and biochemical data were recorded. Results: MTX caused severe cerebellar degeneration in 3 cortical layers, especially the Purkinje layer. The Purkinje layer displayed a disrupted monolayer arrangement with pyknotic nuclei, a significant decrease in cell number, and shrunken cells surrounded by empty spaces. The molecular and granular layers are degenerated with elevated immunoreactions and gene expression of the glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), and neurofilament light chain antibody (NFL). Moreover, MTX significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) while decreasing the levels of reduced glutathione (GSH), serotonin, superoxide dismutase (SOD), acetylcholinesterase (ACHE), norepinephrine, and dopamine. These insults were noticeably mitigated by concomitant treatment with spirulina. Conclusion: Spirulina improves neurological function by modulating the cerebellar damage elicited by MTX. This improvement may be attributed to the anti-inflammatory and antioxidant properties of spirulina. [ABSTRACT FROM AUTHOR]

IntroductionOne goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer's disease (EOAD).MethodsCerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), and YKL-40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.ResultsBiomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP-25, and Ng in EOAD differed significantly from cognitively normal and early-onset non-AD dementia; NfL, YKL-40, and VILIP-1 did not. Across groups, all biomarkers except SNAP-25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP-25 were correlated with at least one cognitive measure.DiscussionThis study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.

BackgroundCharcot–Marie–Tooth disease (CMT), a slowly advancing hereditary nerve disorder, presents a significant challenge in the medical field. Effective drugs for treatment are lacking, and we struggle to find sensitive markers to track the disease’s severity and progression. In this study, our objective was to investigate the levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) in individuals with CMT and to compare them to a control group. Our primary goal is to determine whether these biomarker levels are related to the severity of the disease.MethodsInitially, 44 patients with CMT and 44 controls participated in this study. CMT diagnosis was approved by genetic testing. Disease severity was assessed through clinical evaluations using the CMT Neuropathy Score version 2 (CMTNSv2). NfL and GFAP concentrations were measured using Single molecule array, while FGF-21 and GDF-15 concentrations were measured by enzyme-linked immunosorbent assays.ResultsIn the group of patients with CMT, the concentrations of GDF15, FGF21, NfL, and GFAP were significantly higher than in the control group (p

A growing amount of data has implicated the TOMM40 gene in the risk for Alzheimer’s disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of TOMM40 rs2075650 (‘650) on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of TOMM40 ‘650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of TOMM40 ‘650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of APOE ε4. We found that the TOMM40 ‘650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that TOMM40 ‘650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.

Over 80% of National Football League (NFL) retirees experience daily pain. Pain acceptance is an important psychological construct implicated in the intensity of chronic pain, though these findings have not been extended to NFL retirees. Therefore, the current study examined the association between pain acceptance and pain intensity among former NFL athletes. NFL retirees (N = 90) recruited from 2018 to 2019 completed questionnaires that assessed pain, substance use, and NFL career information. Multiple linear regression examined the association between current pain acceptance and pain intensity while adjusting for other risk factors of pain. NFL retirees reported average scores of 33.31 (SD = 10.00), and 2.18 (SD = 2.40) on measures of pain acceptance and pain intensity, respectively. After covariate adjustment, greater pain acceptance (β = −0.538, p <.001) was associated with lower pain intensity. These findings can further inform the behavioral and mental health care of retired NFL athletes. [ABSTRACT FROM AUTHOR]

BackgroundNeurofilament 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.MethodsWe 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.FindingsIn 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.InterpretationHighly 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.FundingF. Hoffmann-La Roche Ltd.

Background and aimsTo investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).MethodsWe conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.ResultsWe identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.ConclusionsBlood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Abstract Background Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. Objectives To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. Animals 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. Methods Cohort study. Serum NfL concentrations were measured in all dogs using single‐molecule array technology. Results 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. Conclusions and Clinical Importance Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus.

Abstract Convenient and effective biomarkers are essential for the early diagnosis and treatment of Alzheimer’s disease (AD). In the cross-sectional study, 103 patients with AD, 82 patients with aMCI and 508 normal controls (NC) were enrolled. The single‐molecule array (Simoa) technique was used to assess the levels of plasma proteins, including NfL, T-tau, P-tau-181, Aβ40, Aβ42. Montreal Cognitive Assessment (MoCA) was used to assess the overall cognitive function of all subjects. Moreover, Amyloid PET and structural head MRI were also performed in a subset of the population. In the follow-up, the previous 508 normal older adults were followed up for two years, then COX regression analysis was used to investigate the association between baseline plasma proteins and future cognitive outcomes. NfL, T-tau, P-tau-181, Aβ40, Aβ42 and Aβ42/40 were altered in AD dementia, and NfL, Aβ42 and Aβ42/40 significantly outperformed all plasma proteins in differentiating AD dementia from NC, while NfL and Aβ42/40 could effectively distinguish between aMCI and NC. However, only plasma NfL was associated with future cognitive decline, and it was negatively correlated with MoCA (r = − 0.298, p

Abstract Background Grey matter loss is thought to be the primary reason of cognitive disability in MS, with trans-synaptic axonal degeneration acting a supportive role. This research sought to evaluate cognitive profile of Egyptian multiple sclerosis patients and find out if it has a correlation with serum neurofilament or not. Methods This was a cross-sectional research performed on a total of 60 patients with MS and 30 healthy controls. BICAMS battery of neuropsychological tests was used which includes SDMT, CVLT and BVMT. Serum NFLs using ELISA technique. Results Mean ± SD of NFL in RRMS was 82.25 ± 170.9, in PPMS was 22.08 ± 7.26, in SPMS was 95.82 ± 187.5, and in control group was 56.65 ± 125.4, there was high statistical substantial variations among the different groups while there was non-statistical variation between RRMS and PPMS groups, also there was no variation between PPMS and SPMS with regard to serum level of NFL. There is no significant correlation between the NFL and different cognitive tests. Conclusion Since sNfL did not strongly connect with cognitive function in MS patients, it is possible that it cannot be used as a substitute indicator for neuropsychological state in these groups.

Objective: To investigate the effects of hyperbaric oxygen combined with alteplase intravenous thrombolysis on cerebral blood perfusion status and serum ischaemic modified albumin (IMA), neurofilament light chain protein (NFL) and Occludin levels in patients with acute ischemic stroke (AIS). Methods: 124 patients with AIS in our hospital from June 2022 to June 2023 were selected as the study objects, and were randomly divided into control group and observation group, 62 cases in each group. The control group was given alteplase intravenous thrombolysis therapy, and the observation group was given hyperbaric oxygen therapy on the basis of the control group. The clinical efficacy, National institute of Health Stroke Scale (NHISS) and modified Rankin scale (m RS) score, cerebral perfusion status [cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TMax], serum IMA,NFL, Occludin levels and incidence of adverse reactions were compared between the two groups. Results: Compared with control group,the total effective rate of observation group was higher, NHISS and m RS score were decreased after 2 weeks of treatment (P＜0.05). Compared with control group, CBF and CBV were increased and MTT and TMax were shortened in observation group after 2 weeks of treatment (P＜0.05). Compared with control group, serum IMA, Occludin and NFL levels in observation group decreased after 2 weeks of treatment (P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion: Hyperbaric oxygen combined with alteplase intravenous thrombolytic therapy for AIS patients can improve cerebral blood perfusion, reduce serum IMA, Occludin and NFL levels, and alleviate nerve function injury, with significant efficacy and high safety. [ABSTRACT FROM AUTHOR]

The HIV-1 envelope glycoprotein (Env) is the sole neutralizing determinant on the surface of the virus. The Env gp120 and gp41 subunits mediate receptor binding and membrane fusion and are generated from the gp160 precursor by cellular furins. This cleavage event is required for viral entry. One approach to generate HIV-1 neutralizing antibodies following immunization is to express membranebound Env anchored on the cell-surface by genetic means using the natural HIV gp41 transmembrane (TM) spanning domain. To simplify the process of Env trimer membrane expression we sought to remove the need for Env precursor cleavage while maintaining native-like conformation following genetic expression. To accomplish these objectives, we selected our previously developed 'native flexibly linked' (NFL) stabilized soluble trimers that are both near-native in conformation and cleavage-independent. We genetically fused the NFL construct to the HIV TM domain by using a short linker or by restoring the native membrane external proximal region, absent in soluble trimers, to express the full HIV Env ectodomain on the plasma membrane. Both forms of cellsurface NFL trimers, without and with the MPER, displayed favorable antigenic profiles by flow cytometry when expressed from plasmid DNA or mRNA. These results were consistent with the presence of well-ordered cell surface native-like trimeric Env, a necessary requirement to generate neutralizing antibodies by vaccination. Inoculation of rabbits with mRNA lipid nanoparticles (LNP) expressing membrane-bound stabilized HIV Env NFL trimers generated tier 2 neutralizing antibody serum titers in immunized animals. Multiple inoculations of mRNA LNPs generated similar neutralizing antibody titers compared to immunizations of matched NFL soluble proteins in adjuvant. Given the recent success of mRNA vaccines to prevent severe COVID, these are important developments for genetic expression of native-like HIV Env trimers in animals and potentially in humans. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. Methods: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. Results: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p =.002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p =.034 and β = 0.30, p =.013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p =.002) and AD pathology (AUC 0.78 to 0.87, p =.010), but not of cognitive decline (AUC 0.79 to 0.85, p =.081). Conclusion: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people. [ABSTRACT FROM AUTHOR]

Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype. [ABSTRACT FROM AUTHOR]

Increased choroid plexus (CP) volume has been recently implicated as a potential predictor of worse multiple sclerosis (MS) outcomes. The biomarker signature of CP changes in MS are currently unknown. To determine the blood-based biomarker characteristics of the cross-sectional and longitudinal MRI-based CP changes in a heterogeneous group of people with MS (pwMS), a total of 202 pwMS (148 pwRRMS and 54 pwPMS) underwent MRI examination at baseline and at a 5-year follow-up. The CP was automatically segmented and subsequently refined manually in order to obtain a normalized CP volume. Serum samples were collected at both timepoints, and the concentration of 21 protein measures relevant to MS pathophysiology were determined using the Olink™ platform. Age-, sex-, and BMI-adjusted linear regression models explored the cross-sectional and longitudinal relationships between MRI CP outcomes and blood-based biomarkers. At baseline, there were no significant proteomic predictors of CP volume, while at follow-up, greater CP volume was significantly associated with higher neurofilament light chain levels, NfL (standardized β = 0.373, p = 0.001), and lower osteopontin levels (standardized β = −0.23, p = 0.02). Higher baseline GFAP and lower FLRT2 levels were associated with future 5-year CP % volume expansion (standardized β = 0.277, p = 0.004 and standardized β = −0.226, p = 0.014, respectively). The CP volume in pwMS is associated with inflammatory blood-based biomarkers of neuronal injury (neurofilament light chain; NfL) and glial activation such as GFAP, osteopontin, and FLRT2. The expansion of the CP may play a central role in chronic and compartmentalized inflammation and may be driven by glial changes. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. Objective s : To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. Animals: 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. Methods: Cohort study. Serum NfL concentrations were measured in all dogs using single‐molecule array technology. Results: 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. Conclusions and Clinical Importance: Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus. [ABSTRACT FROM AUTHOR]

Background: Grey matter loss is thought to be the primary reason of cognitive disability in MS, with trans-synaptic axonal degeneration acting a supportive role. This research sought to evaluate cognitive profile of Egyptian multiple sclerosis patients and find out if it has a correlation with serum neurofilament or not. Methods: This was a cross-sectional research performed on a total of 60 patients with MS and 30 healthy controls. BICAMS battery of neuropsychological tests was used which includes SDMT, CVLT and BVMT. Serum NFLs using ELISA technique. Results: Mean ± SD of NFL in RRMS was 82.25 ± 170.9, in PPMS was 22.08 ± 7.26, in SPMS was 95.82 ± 187.5, and in control group was 56.65 ± 125.4, there was high statistical substantial variations among the different groups while there was non-statistical variation between RRMS and PPMS groups, also there was no variation between PPMS and SPMS with regard to serum level of NFL. There is no significant correlation between the NFL and different cognitive tests. Conclusion: Since sNfL did not strongly connect with cognitive function in MS patients, it is possible that it cannot be used as a substitute indicator for neuropsychological state in these groups. [ABSTRACT FROM AUTHOR]

In general, financial markets of limited attention or visibility are expected to exhibit more inefficient asset prices. Such markets thus require eventual, increased trading to resolve these inefficiencies. In this study, we consider this financial framework within the sports gambling market for National Football League (NFL) games. We consider whether NFL games garnering less public attention are more likely to see larger movements in their betting lines. We consider games with smaller television audiences, with kickoff times shared with other contests, and between teams with smaller fanbases, to be indicative of less visibility. To test our model, we collected betting line data for all regular and postseason NFL football games from 2007–2021. Based on a sample of 3,756 games, our findings indicate more frequent and larger line movements in games with indications of less widespread attention, and many of these results are statistically significant. Our conjecture is that such differences in line movement levels may derive from the limited resources of oddsmakers being disproportionately focused on games with the most visibility. [ABSTRACT FROM AUTHOR]