Intermediate Filaments - Science topic

Background Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic AL...

Background and Purpose To date, no previous studies have used multishell diffusion MRI to identify striatal microstructural damage in vivo in amyotrophic lateral sclerosis (ALS) patients. Thus, in the present study, we aimed to comprehensively explore connectivity‐based selective striatal subregion microstructural damage in sporadic ALS patients an...

In this narrative review, we address mild cognitive impairment, a frequent complication of Parkinson’s disease (PD) and atypical parkinsonian disorders (APDs). Recent diagnostic criteria have blurred the lines between PD and dementia with Lewy bodies (DLB), particularly in the cognitive domain. Additionally, atypical parkinsonian syndromes like pro...

Serum Neurofilament Chains in Multiple Sclerosis

Objective This study explored how the weight-adjusted waist index (WWI) and a body shape index (ABSI) are related to serum neurofilament light chain (sNfL) levels among U.S. adults. We aimed to evaluate sNfL, which plays key roles in neuronal injury in neurological diseases, given its understudied connection to obesity. Methods We used cross-secti...

Hepatitis C virus (HCV) is a major human pathogen causing liver diseases. Although direct‐acting antiviral agents effectively inhibit HCV infection, cell–cell transmission remains a critical venue for HCV persistence in vivo. However, the underlying mechanism of how HCV spreads intercellularly remains elusive. Here, we demonstrated that vimentin, a...

Objective Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosoma...

INTRODUCTION The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid‐positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid‐β. METHODS Linear mixed‐...

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterised by a high prevalence of sporadic cases. Various molecular mechanisms are involved in its pathogenesis. This pilot study aimed to identify potential risk and protective human leukocyte antigen (HLA) alleles in PD, discover candidate alleles for further research, and e...

INTRODUCTION Alzheimer's disease (AD) is a highly heritable disease (60%–80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers. METHODS Blood concentrations o...

Alzheimer’s Disease (AD) is a complex polygenic neurodegenerative disorder. Its genetic risk’s relationship with all-cause dementia may be influenced by the plasma proteome. Up to 40,139 UK Biobank participants aged ≥ 50y at baseline assessment (2006–2010) were followed-up for ≤ 15 y for dementia incidence. Plasma proteomics were performed on a sub...

Although cytoplasmic intermediate filaments (cIFs) are essential for cell physiology, the molecular and cell functional consequences of cIF disturbances are poorly understood. Identifying defaults in cell function-controlled tissue homeostasis and understanding the interrelationship between specific cIFs and distinct cell functions remain key chall...

The endoplasmic reticulum (ER) is a dynamic and continuous membrane network with roles in many cellular processes. The importance and maintenance of ER structure and function have been extensively studied in interphase cells, yet recent findings also indicate crucial roles of the ER in mitosis. During mitosis, the ER is remodelled significantly wit...

Our objective was to evaluate the individual and combined prognostic attributes of baseline serum and CSF measurements of Neurofilament light chain (sNfL, cNfL) and glial fibrillary acidic protein (sGFAP, cGFAP) on long term clinical outcomes in MS. In this retrospective single center study, patients with serum and CSF stored at first MS presentati...

Background The relationships of serum neurofilament light chain (NfL) levels with chronic kidney disease (CKD) and renal function indicators remain controversial, and comprehensive studies with large sample sizes are lacking. Methods In total, 2,051 participants aged 20 to 75 years were identified from the National Health and Nutrition Examination...

Background The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer’s disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1,...

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...

INTRODUCTION Both micro‐ and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following...

Background: Concentrations of neurofilament light chain (NfL), a neuroaxonal damage marker, increase with age. Therefore, age-dependent reference values are important in clinical practice. However, so far these have only been established with a bead based system and age-dependent z-scores for CSF are missing. In addition, we here propose how the co...

Background To establish simple screening tests to suspect Alzheimer’s disease (AD) pathology, the clinical sign “head-turning sign” (HTS), which is a patient’s behavior of turning their head towards their partner to seek assistance with questions posed by the examiner during the interview, and the simple screening questionnaire for dementia named “...

We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (n = 10) and wild‐type (n = 8) mice, as models of intrinsically ‘low’ and ‘normal’ AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromat...

Intermediate filaments (IFs) are a key component of the cytoskeleton, essential for regulating cell mechanics, maintaining nuclear integrity, positioning organelles, and modulating cell signaling. Unlike actin filaments and microtubules, IFs have slower dynamics, and current insights into IF function primarily come from studies using long-term pert...

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, qu...

Background Western countries have provided reference values (RV) for Alzheimer’s disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective We provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament li...

Diabetic retinopathy (DR) is one of the most common complications of diabetes and induces severe visual impairment worldwide. Endothelial cell dysfunction plays an important role in the pathogenesis of DR. Here, we keep a watchful eye on α/β-hydrolase domain–containing 1 (ABHD1), a potential regulator in lipid metabolism and neovascularization. Res...

Diacetylmorphine abuse is a major social problem that jeopardizes the world, and abuse can cause serious neurological disorders. Apoptosis plays an important role in neurological diseases. A previous study by our group found that the brain tissue of diacetylmorphine-addicted rats showed severe vacuole-like degeneration and increased apoptosis, but...

The clinical spectrum of Alzheimer’s disease (AD) ranges dynamically from asymptomatic and mild cognitive impairment (MCI) to mild, moderate, or severe AD. Although a few disease-modifying treatments, such as lecanemab and donanemab, have been developed, current therapies can only delay disease progression rather than halt it entirely. Therefore, t...

Background Advances in instrumented mouthguards (iMGs) allow for accurate quantification of single high-acceleration head impacts and cumulative head acceleration exposure in collision sports. However, relationships between these measures and risk of brain cell injury remain unclear. Aim The purpose of this study was to quantify measures of non-co...

INTRODUCTION Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized. METHODS Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal...

Background and purpose The purpose was to explore the prognostic utility of neurofilament light chain (NfL) in patients with immune‐mediated polyradiculoneuropathies (IMPs). Methods This retrospective monocentric study analysed serum and cerebrospinal fluid samples from patients diagnosed with IMP collected prior to treatment initiation. NfL conce...

BACKGROUND Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)‐derived measurements in Alzheimer's disease (AD) remain unclear. METHODS In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40...

Objective To describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti‐Hu) autoimmunity. Methods A retrospective review of patients with ANNA1‐IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups ba...

From the day we are born, the nervous system is subject to insult, disease and degeneration. Aberrant phosphorylation states in neurofilaments, the major intermediate filaments of the neuronal cytoskeleton, accompany and mediate many pathological processes in degenerative disease. Neuronal damage, degeneration and death can release these internal c...

The heterogeneity of Parkinson’s disease (PD) has been recognized in clinical, with patients categorized into distinct subsets based on motor phenotype, such as tremor-dominant PD (TD), postural instability and gait difficulty-dominant PD (PIGD) and mixed PD (Mix). Despite this categorization, the underlying mechanisms of this heterogeneity remain...

Disease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. H...

Background Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage. Objective To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occu...

To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diag...

Vimentin is a type III intermediate filament (IF) protein, that is induced in a large number of solid tumours. A single cysteine at position 328 in vimentin plays a crucial role in assembly, organisation and stability of IFs. However, its exact function during epithelial mesenchymal transition (EMT) and cancer progression has not been investigated....

Background and Objectives: The objective of the study is to determine whether there is a difference in physical therapy outcomes in patients with cervical and/or lumbar pain who have insomnia compared to patients without insomnia during a two-week period of active treatment under the conditions of routine clinical practice. Materials and Methods: T...

Hagfish intermediate filament (HIF) proteins, consisting of α and γ subunits, have been previously recombinantly expressed, purified, and utilized to form dry fibers with impressive mechanical properties. HIFα and HIFγ consist of three protein domains (N-termini, C-termini, and central rod domain). To begin to understand the structure–function rela...

Background The effects of intraoperative permissive hypercapnia (PaCO2 of 45–55 mmHg) on the central nervous system remain unclear. Neurofilament light chain (NfL, a protein found in the axons and nerve fibers of neurons) has been associated with central nervous system disorders. This study investigated the effect of intraoperative permissive hyper...

Desmin intermediate filaments play a crucial role in stress transmission and mechano-protection. The loss of its integrity triggers myofibril breakdown and muscle atrophy for which desmin phosphorylation (pDes) is a priming factor. We investigated whether eccentric accentuated resistance exercise (RE) influences the regulation of pDes, effecting it...

Introduction Peripheral neurofilament light chain (NfL) reflect neuronal and axonal damage. Most studies have been focused on NfL cerebrospinal fluid measures since peripheral levels were difficult to detect. However, with recent advent of single molecule array (SIMOA) technology, NfL is now detectable peripherally at small concentrations (pg/ml)....

Blood‐based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS‐AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodeg...

Neurodegenerative diseases, such as Alzheimer’s disease (AD), are a growing public health crisis, exacerbated by an aging global population and the lack of effective early disease-modifying therapies. Early detection of neurodegenerative disorders is critical to delaying symptom onset and mitigating disease progression, but current diagnostic tools...

INTRODUCTION We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)‐independent or Aβ‐dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET). METHODS A total of 2935 participants underwent blood sampling for measurements of plasma Aβ42...

Objective To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing–remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response. Methods Multicenter prospective study including 115 RRMS patients initiating ocrelizumab tr...

Background Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AI...

A microphysiological system (MPS) is an in vitro culture technology that reproduces the physiological microenvironment and functionality of humans and is expected to be applied for drug screening. In this study, we developed an MPS for the structured culture of human iPSC-derived sensory neurons and then predicted drug-induced neurotoxicity by morp...

Emerging evidence suggests that repetitive negative thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. Given that women have a greater risk of many neurodegenerative diseases, this study investigated whether worry and brooding are associated with general neurodegeneration and whether associatio...

Neurofilaments are intermediate filaments present in neurons. These provide structural support and maintain the size and shape of the neurons. Dysregulation, mutation, and aggregation of neurofilaments raise the levels of these proteins in the blood and cerebrospinal fluid (CSF), which are characteristic features of axonal damage and certain rare n...

Plasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological me...

Importance: While apathy and affective neuropsychiatric symptoms (NPS) are common in the clinical spectrum of Alzheimer's disease (AD), their neurobiological correlates remain unclear. Objective: To longitudinally examine plasma markers of neurodegeneration (neurofilament light chain; NfL) and tau pathology (phosphorylated at threonine 181; p-tau18...

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterised by a high prevalence of sporadic cases. Various molecular mechanisms are involved in its pathogenesis. This pilot study aimed to identify potential risk and protective human leukocyte antigen (HLA) alleles in PD, discover candidate alleles for further research, and e...

Objective To study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results. Methods We analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women an...

This narrative review explores the current landscape of blood biomarkers in Frontotemporal dementia (FTD). Neurofilament light chain (NfL) may be useful in the differentiation of behavioral variant FTD from primary psychiatric disorders (PPDs) or dementia with Lewy bodies (DLB). In prodromal FTD and presymptomatic mutation carriers (GRN, MAPT, C9or...

Background: The assessment of serum neurofilament light chain (sNfL) is increasingly significant in the field of neurology. In multiple sclerosis (MS), it proves valuable as a marker for monitoring disease activity and treatment response. Objective: To compare the Simoa and Lumipulse platforms for measuring sNfL and to establish age-specific refere...

Background: Cognitive decline (CD) is a significant concern in Parkinson's disease (PD), highlighting the need for reliable risk prediction models for early intervention. This study used machine learning (ML) techniques to predict the CD risk over five-year in early-stage PD. Methods: Data from the Early Parkinson's Disease Longitudinal Singapore (...

Introduction: Primitive neuroectodermal tumours are a family of neoplasms that derive from the neural crest. They are classified into 3 groups: 1) central PNET, 2) Neuroblastoma and 3) peripheral PNET in peripheral nerves. The aim is to describe the characteristics of the case of a 32-year-old female patient who presented with an inguinal tumour wi...