SEARCH · Search PubMed

Results for “Neurofilament light”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2025

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders.

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. RESULTS: Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. CONCLUSIONS: Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

Humans↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed2025

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer's disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1-7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer's disease cohort included 35 adults with sporadic Alzheimer's disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting 'pro-youthful' levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer's disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer's disease and related dementias and warrant further investigation.

Alzheimer’s disease↗

PubMed2026

Astragalus membranaceus therapy in patients with spinocerebellar ataxia type 3.

BACKGROUND AND AIM: Spinocerebellar ataxia type 3 (SCA3) is the most common form of hereditary cerebellar ataxia. The insulin/insulin-like growth factor 1 (IGF1) system (IIS) has been proposed as a potential target for disease-modifying therapy. Astragalus membranaceus (AM) may modulate the IIS pathway and reduce neurodegeneration, as indicated by plasma neurofilament light chain (NfL), a biomarker of disease progression. EXPERIMENTAL PROCEDURE: A randomized, triple-blind, placebo-controlled crossover trial was conducted in 32 patients with SCA3. Participants received AM or placebo for three months, followed by a one-month washout, then crossed over to the alternate treatment. Plasma NfL and IIS-related markers were measured. Twenty-three participants completed the trial. RESULTS AND CONCLUSION: Intention-to-treat analysis revealed a modest within-treatment reduction in NfL levels (27.6 ± 10.7 vs. 25.6 ± 9.8 pg/mL, P = 0.040) and increased insulin (12.5 ± 15.2 vs. 21.1 ± 15.5 μIU/mL, P = 0.004) after AM. However, the adjusted regression model showed no significant between-treatment difference in NfL (P = 0.127), and changes in NfL were not correlated with insulin. No significant changes were observed in IGF1 or IGF-binding proteins. Exploratory subgroup analyses suggested larger biomarker changes in later-stage patients. No carryover effects or demographic differences were noted. Overall, AM administration was associated with modest within-treatment biomarker changes in NfL and insulin, although the adjusted between-treatment difference in NfL was not statistically significant. These findings should be interpreted cautiously as preliminary and hypothesis-generating observations rather than confirmatory evidence of therapeutic efficacy.

Astragalus membranaceus↗

PubMed2026

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n = 48), meningitis (TI-; n = 80), (cranial) nerve palsies/polyradiculitis (PND; n = 61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p < 0.001/sGFAP p = 0.0083; CSF-NfL p = 0.003/sNfL p = 0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p = 0.0049/sGFAP p = 0.003). The overall group effect (p ≤ 0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p = 0.012/sNfL p = 0.002; CSF-GFAP p < 0.0001/CSF-NfL p = 0.0001), which also predicted unfavorable outcome at discharge (sGFAP p = 0.006/sNfL p = 0.004; CSF-GFAP p = 0.003/CSF-NfL p = 0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans↗

PubMed2025

Quantitative proteomic analysis of the brain reveals the potential antidepressant mechanism of Jiawei Danzhi Xiaoyao San in a chronic unpredictable mild stress mouse model of depression.

OBJECTIVE: To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan (,JD) in chronic unpredictable mild stress (CUMS)-induced depression in mice. METHODS: Using the CUMS mouse model of depression, the antidepressant effects of JD were assessed using the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Tandem mass tag (TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment. Hierarchical clustering, Gene Ontology function annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interactions (PPIs) were used to analyze differentially expressed proteins (DEPs), which were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: Behavioral tests confirmed the anti-depressant effects of JD, and bioinformatics analysis revealed 59 DEPs, including 33 up-regulated and 26 down-regulated proteins, between the CUMS and JD-M groups. KEGG and PPI analyses revealed that neuro-filament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression. qRT-PCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light (NEFL) and medium (NEFM) and inhibited the phosphorylation of extracellular regulated kinase 1/2 (ERK1/2), whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM. CONCLUSIONS: The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.

Animals↗

PubMed2025

Correlation of extracellular vesicle Alu RNA with brain aging and neuronal injury: a potential biomarker for brain aging.

BACKGROUND: Extracellular vesicles (EVs) are promising biomarkers for neurodegeneration. Alu elements are retrotransposons increasingly expressed with age and may be involved in aging-related diseases. OBJECTIVE: To determine the potential of Alu RNA in plasma-derived EVs as a biomarker for brain aging and neuronal injury. METHODS: EVs were isolated from plasma samples across different age groups. EV Alu RNA levels were measured and their associations with biomarkers of brain aging, including plasma neurofilament light chain (NfL), plasma amyloid-beta (Aβ42 and Aβ40), and plasma phosphorylated tau (p-Tau181), were analyzed. RESULTS: EV Alu RNA levels were increased significantly with age and were strongly correlated with plasma NfL, suggesting a strong association between EV Alu RNA and neuronal injury. Significant correlations were also found between EV Alu RNA and plasma amyloid-beta levels, while no significant association was observed with tau pathology. CONCLUSIONS: EV Alu RNA levels are elevated with age and associated with neuronal injury, highlighting their potential as a novel, non-invasive biomarker for brain aging and neurodegeneration.

Humans↗

PubMed2026

Longitudinal functional network connectivity changes across the clinical stages of C9orf72 hexanucleotide repeat expansion carriers.

INTRODUCTION: Intrinsic functional connectivity network abnormalities in C9orf72 hexanucleotide repeat expansion carriers emerge during the asymptomatic phase, yet longitudinal studies remain limited. We examined cross-sectional abnormalities and longitudinal connectivity changes across clinical stages. METHODS: We analyzed task-free functional magnetic resonance imaging (fMRI) and structural MRI data in 36 asymptomatic (aSxC9), 17 prodromal (proC9), and 29 symptomatic (SxC9) carriers, and 107 healthy controls (HCs). Functional networks previously found altered in C9orf72, including salience, sensorimotor, default mode, and medial pulvinar thalamic networks, were examined. Associations between longitudinal connectivity and gray matter decline with baseline neurofilament light chain (NfL) concentrations and symptom severity were assessed. RESULTS: aSxC9 and SxC9 showed longitudinal connectivity changes within specific networks. In aSxC9, connectivity changes correlated with baseline NfL. In proC9 and SxC9, changes in connectivity and gray matter were associated with baseline NfL and symptom severity. DISCUSSION: C9orf72 expansion carriers demonstrate stage-specific network connectivity changes.

Humans↗

PubMed2025

Elevated plasma GFAP levels in MCI link APOE ε4 allele with impaired gait speed.

The presence of at least one copy of the apolipoprotein ε4 allele (APOE ε4) is a known predictor of gait impairment risk among older adults. However, the mechanisms by which APOE ε4 affects gait performance remain unclear. This cross-sectional study aimed to reveal underlying pathological mechanisms linking APOE ε4 carriage to slow gait. This secondary analysis used baseline assessments from the J-MINT multicenter intervention trial, focusing on older adults with mild cognitive impairment. Gait speed was measured at baseline, with slow gait (SG) defined as speeds one standard deviation below the age- and sex-specific mean. APOE phenotype and plasma biomarkers related to Alzheimer's disease (AD), including amyloid-β composite biomarker, phosphorylated Tau 181, neurofilament light, and glial fibrillary acidic protein (GFAP), were also measured. The analysis included 236 non-APOE ε4 carriers and 84 carriers of at least one APOE ε4. APOE ε4 carriers exhibited significantly slower gait speed than non-carriers (1.20 m/s [SD = 0.22] vs 1.26 m/s [SD = 0.23], p = 0.042). Significant interaction between APOE ε4 carriage and SG was observed only in plasma GFAP levels (F1, 312 = 7.17, p = 0.008), indicating that individuals with APOE ε4 and SG had significantly higher plasma GFAP levels. Elevated plasma GFAP levels fully mediated the association between APOE ε4 carriage and gait speed (partially standardized indirect effect = -0.059: -0.12 to -0.013]). No other AD-related biomarkers mediated this association. Our results suggest that APOE ε4-related gait changes may reflect AD pathology, as indicated by elevated GFAP levels, and could potentially accelerate dementia symptoms.

Aged↗

PubMed2026

Tau proteoforms as plasma biomarkers in Alzheimer's disease: mechanisms, measurement, and medicine.

INTRODUCTION: Blood-based tau proteoforms have emerged as specific, scalable biomarkers of Alzheimer's pathology, addressing the limitations of symptom-based diagnosis, neuroimaging, and invasive cerebrospinal fluid (CSF) testing. This review synthesizes advances in tau phosphorylation and truncation biology, evaluates translation from CSF to plasma with state-of-the-art proteomics, and outlines the analytical standards and cross-matrix calibration needed for clinical adoption. AREAS COVERED: We conducted a literature search in PubMed and Google Scholar. We reviewed studies published between January 2005 and September 2025 investigating tau proteoforms in Alzheimer's disease. EXPERT OPINION: Blood-based tau proteoforms are poised to move Alzheimer's diagnostics from specialized imaging to accessible frontline testing, with plasma p-tau217 approaching positron emission tomography (PET) and CSF performance and multi-analyte panels with glial fibrillary acidic protein (GFAP) or neurofilament light (NfL) improving differential diagnosis while reducing invasiveness and cost. Building on the first FDA-cleared plasma assay (Lumipulse G p-tau217/Aβ1-42 Ratio) in May 2025, we anticipate a dual pathway over the next decade in which referral centers use high-plex mass spectrometry (MS) panels for phosphoforms and truncations, while primary care adopts automated high-throughput immunoassays (e.g. chemiluminescent enzyme immunoassay (CLEIA)) for triage, supported by harmonized standard operating procedures (SOPs), cross-matrix calibration, and robust reference materials.

Humans↗

PubMed2026

The HTT1a protein initiates HTT aggregation in a knock-in mouse model of Huntington's disease.

The mutation that causes Huntington's disease is a CAG repeat expansion in exon 1 of the huntingtin gene (HTT) that leads to an abnormally long polyglutamine tract in the huntingtin protein (HTT). Mutant CAG repeats are unstable and increase in size in specific neurons and brain regions with age, a phenomenon that constitutes the first step in the pathogenesis of the disease. In the presence of an expanded CAG repeat, cryptic polyadenylation (polyA) sites in intron 1 of the HTT pre-mRNA can become activated leading to the polyadenylation of a prematurely terminated transcript, HTT1a. This encodes the HTT1a protein, which is known to be very aggregation-prone and highly pathogenic. Given that the longer the CAG repeat the more HTT1a is generated, could the production of HTT1a be the mechanism through which somatic CAG repeat expansion exerts its pathogenic consequences? Resolving this issue is very important for the design of therapeutic approaches to lower huntingtin levels. We have used a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 approach to prevent the production of HTT1a in a knock-in mouse model of Huntington's disease. All potential cryptic polyA sites were deleted from Htt intron 1 in HdhQ150 mice and colonies were established that were heterozygous for the intron 1 deletion on a mutant allele (HdhQ150ΔI) and heterozygous for the deletion on a wild-type allele (WTΔI). The CAG repeat sizes in the HdhQ150 and HdhQ150ΔI colonies were well-matched at approximately 195 CAGs. As predicted, the deletion of the cryptic polyA sites from Htt intron 1 prevented the generation of the Htt1a transcript in the HdhQ150ΔI mice. However, very low levels of the HTT1a protein were detected, which resulted from a Htt readthrough product of exon 1 and exon 2, that had retained the deleted intron and terminated at a cryptic polyA site in intron 2. HdhQ150, HdhQ150ΔI, wild-type and WTΔI mice were studied until 17 months of age. Immunohistochemical and homogeneous time-resolved fluorescence analysis showed that HTT aggregation in both HdhQ150 and HdhQ150ΔI brains contained HTT1a, but the dramatic decrease in soluble HTT1a levels in HdhQ150ΔI brains delayed the appearance of aggregated HTT1a by several months. Although this delay in aggregate pathology only partially reversed transcriptional dysregulation, the biomarkers neurofilament light polypeptide (NEFL) and breast regression protein 39 (BRP39) (YKL40) remained at wild-type levels in HdhQ150ΔI mice at 17 months of age. These data demonstrate that the production of HTT1a initiates HTT aggregation and that it is important to target HTT1a in huntingtin-lowering therapeutic strategies.

Animals↗

PubMed2026

Genotype-structure-phenotype correlations define divergent natural history in early-onset spastic paraplegia type 4.

Hereditary spastic paraplegia type 4 (SPG4), caused by variants in SPAST, is the most common form of HSP and exhibits a remarkable phenotypic heterogeneity ranging from late-onset pure presentations to severe, early-onset complex disease. Robust genotype-phenotype correlations and detailed natural history data are lacking, limiting clinical trial readiness. We analyzed 206 patients with genetically confirmed SPG4 enrolled across seven international centers, complemented by high-quality literature-derived cases. Deep phenotyping included standardized motor scales, spasticity ratings, developmental milestones, and patient-reported outcomes. We developed an extended essentiality-mapping framework to classify SPAST missense variants by integrating in silico pathogenicity predictions, evolutionary constraint, physicochemical residue connectivity, and variant enrichment within the human spastin hexamer structure. Plasma neurofilament light chain (pNfL) using was quantified using Simoa in 26 patients and 101 controls. We identified 136 distinct SPAST variants, including 10 novel variants. Variant class segregated strongly by inheritance, with de novo cases enriched for missense variants and inherited cases showing a variety of variant classes with enrichment for truncating variants. Longitudinal analysis revealed two latent trajectories: a rapidly progressive severe subgroup enriched for de novo missense variants, and a biphasic moderate subgroup enriched for inherited truncating variants. Patient stratification integrating spastin essentiality mapping (missense variants affecting essential, neutral, or context-dependent residues) with established genetic modifiers (biallelic pathogenic variants or modifier variants in trans) classified patients into predicted severe and moderate subgroups with divergent age at onset and clinical disease progression. The severe subgroup showed early developmental delays, rapid loss of ambulation, and declining quality of life, while the moderate subgroup displayed delayed but accelerating disease progression. pNfL levels were elevated in both subgroups, most pronounced in severe early disease. This study provides the most detailed natural history of SPG4 to date and introduces a biologically informed stratification framework that links variant class and location to divergent clinical trajectories. These data establish clinically meaningful benchmarks and offer a genotype-based framework to improve anticipatory care and optimize trial design for SPG4.

SPAST↗

PubMed2026

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid α-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient ≤66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score ≥7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article↗

PubMed2025

Emerging biomarkers in ischemic stroke.

Ischemic stroke is a devastating global public health problem and the leading cause of acute death and chronic disability. Despite being the diagnostic cornerstone, limitations in neuroimaging, including availability, cost, and therapeutic window, have rekindled interest in biomarker-based approaches. Biomarkers will be employed to facilitate the eventual prediction, early diagnosis, and prognosis of strokes, as well as to inform person-centered medicine. This review summarizes recent advances in the search for biomarkers related to inflammatory, endothelial, metabolic, and neuroaxonal pathways. Interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), endothelial microparticles (EMP), and homocysteine serve as predictive biomarkers corresponding to vascular risk and inflammatory priming. Glial fibrillary acidic protein (GFAP), D-dimer, and neuron-specific enolase (NSE) are diagnostic markers that can already subtype stroke and estimate lesion burden. Prognostic biomarkers, such as serum neurofilament light chain (sNfL), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), and growth differentiation factor 15 (GDF-15), are associated with infarct size and long-term outcomes. The -omic sciences (genomic, proteomic, and metabolomic) have discovered defined molecular signatures and panels with high specificity to describe heterogeneity in stroke. Cerebrospinal fluid (CSF) biomarkers and newer imaging modalities, such as those provided through positron emission tomography/computed tomography (PET/CT), offer valuable adjuncts to blood biomarkers in the diagnosis of conditions. Translational potential is hindered by heterogeneity in the transcriptional landscape.

Ischemic stroke↗

PubMed1977

Neurofilamentous changes in goldfish (Carassius auratus L.) brain in relation to environmental temperature.

The presence of neurofilaments in the synaptic boutons in the brains of goldfish maintained at 5 degrees C for 177 days or more is reported. Neurofilaments are not found in boutons of control fish kept at 15degreesC. It is suggested that the neurofilaments may be equated with neurofibrillary rings seen by light microscopy. Neurofilaments have been implicated in axoplasmic transport and, therefore, irregularities in the occurrence or appearance of these filaments may reflect alterations in their functions. The unusual occurrence of neurofilaments in the boutons of cold temperature goldfish may be an expression of early degenerative changes or may represent a modification of axoplasmic transport. The suitability of goldfish as a model for the study of the functional effects of neurofibrillary/neurofilamentous accumulations is discussed.

Animals↗

PubMed1975

Ultrastructure of the joint receptors of the tortoise (Testudo graeca. Emys orbicularis).

The ultrastructure of the spray-like ramified encapsulated corpuscles with the primitive inner core from the joint capsules of the large limb joints of the tortoise (Testudo graeca and Emys orbicularis) was examined. Each of the branches of the receptor consists of three components. Through the middle of the receptor branche runs the nerve terminal, containing in the receptor matrix numerous mitochondria, tiny light vesicles and neurofilaments and neurotubules running in the axial way. The nerve terminal gives off on some places among the inner core cells tiny finger-like processes. The axon is surrounded by the inner core cells and their irregular plasmatic processes. Among the inner core cells and their irregular plasmatic processes there is a labyrinth of spaces, connected centrally with the periaxonal space and with the boundary space on the periphery. The inner core cells are covered on the surface, turning to the boundary space by the basal membrane. The inner core has a very primitive structure, it still lacks the typical lamellar structure. The capsule of the receptor is formed by flat cells, which surround the inner core in 1--3 layers. Between the capsule of the receptor and the inner core is the boundary space, containihg sporadical collagenous fibrils. The structure of the spray-like ramified encapsulated corpuscles with the primitive inner core from the joint capsules of the tortoise is analogous to the simple lamellar receptors from the skin of some reptiles (Von Düring 1973, 1974). The primitive structure of the inner core of the joint receptors in the tortoise reminds of the structure of the inner core of the developing simple (paciniform) corpuscles (Poláĉek and Halata 1970) and Pacinian corpuscles (Malinovský 1974). The observed nerve endings represent a primitive, early stage in phylogeny development of the lamellar mechanoreceptors.

Animals↗

PubMed1979

Immunohistochemical localization of neurofilament antigen in rat cerebellum.

The distribution of neurofilaments in the rat cerebellar cortex was studied by immunoperoxidase histochemistry using an antiserum raised against neurofilaments isolated from brain (anti-NF). In light microscope preparations, this antiserum selectively stained known neurofilament-containing structures. Staining was most intense in myelinated axons of the white matter and in the terminal branches of basket cell axons. No staining was apparent in either neuronal or glial cell bodies or in glial cell processes. These findings were confirmed in electron microscopic preparations of the same material. Neurofilaments stained by the antiserum were abundant in basket cell axons and also occurred in small bundles in mossy fibre terminals. Adjacent microtubules were not stained by the antiserum. There was no evidence of stained cytoplasmic filaments in glial cell processes. Thus it appears that neurofilaments contain unique antigens which do not occur in either microtubules or in glial cytoplasmic filaments. The antiserum did not induce staining of synaptic junctional structures, a result which contradicts previous suggestions that neurofilaments are structural components of synaptic densities.

Animals↗

PubMed1975

Neurofilament and glycogen changes during cold acclimation in the trochlear nucleus of lizards (Sceloporus undulatus).

In lizards (Sceloporus undulatus), long term (13 or 19 weeks) acclimation to an environment of 6 degrees C produces a striking increase in the argyrophilic neurofibrillar network in most large perikarya of the trochlear nucleus. In electron micrographs the cells contain numerous bundles of 10-30 regularly-spaced 90 A neurofilaments. In the cells from warm acclimated animals, a plexus of neurofibrils is seen by light microscopy. The electron micrographs show scattered neurofilaments and fewer, thinner bundles than in the cold. Within the cell bodies of the cold animals, glycogen particles are organized in regional accumulations from which other organelles are excluded except for the bundles of neurofilaments which are distributed throughout the cytoplasm. The aggregations of rough endoplasmic reticulum (RER) are also penetrated by the neurofilament bundles. The increased neurofilamentous network in the cold is not accompanied by obvious changes in the amount or distribution of RER or of microtubules which are present in limited numbers in both conditions. The dendrites of trochlear cells and axon terminals within the nucleus also show a cold induced increase in neurofilaments, as well as in the distinctive accumulations of glycogen particles.

Acclimatization↗