Serum Glial Fibrillary Acidic Protein Levels Research Articles

Utility of serum neurofilament light chain and glial fibrillary acidic protein as diagnostic biomarkers of freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is one of the most distressing features of Parkinson’s disease (PD), increasing the risks of fractures and seriously affecting patients’ quality of life. We aimed to examine the potential diagnostic roles of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in PD patients with FOG (PD-FOG). We included 99 patients, comprising 54 PD patients without FOG (PD-NoFOG), 45 PD-FOG and 37 healthy controls (HCs). Our results indicated serum markers were significantly higher in PD-FOG and postural instability and gait difficulty (PIGD) motor subtype patients than in PD-NoFOG and non-PIGD subtype patients (P < 0.05), respectively. Patients with high concentrations of the markers NFL and GFAP had higher PIGD scores and greater FOG severity than those with low concentrations. Moreover, serum levels of both NFL and GFAP were significantly positively associated with age, FOG severity, PD-FOG status, and negatively associated with Mini-Mental State Examination (MMSE) scores. Logistic regression analysis identified serum levels of NFL and GFAP as independent risk factors for PD-FOG. Mediation analysis revealed that MMSE scores fully mediated the relationship between serum GFAP levels and FOG-Q scores, accounting for 33.33% of the total effects (indirect effect = 0.01, 95% CI 0.01–0.02). NFL levels differentiated PD-FOG from PD-NoFOG with reliable diagnostic accuracy (AUC 0.75, 95% CI 0.66–0.84), and the combination of NFL, GFAP, duration and MMSE scores demonstrated high accuracy (AUC 0.84, 95% CI 0.76–0.91). Our findings support the notion that NFL and GFAP may be potential biomarkers for the diagnosis of PD-FOG.

High burdens of phosphorylated tau protein and distinct precuneus atrophy in sporadic early-onset Alzheimer’s disease

Early-onset Alzheimer’s disease (EOAD) is a rare devastating subclassification of Alzheimer’s disease (AD). EOAD affects individuals <65 years old, and accounts for 5%–10% of all AD cases. Previous studies on EOAD primarily focused on familial forms, whereas research on sporadic EOAD (sEOAD), which represents 85%–90% of EOAD cases, is limited. In this prospective cohort study, participants were recruited between 2018 and 2023 and included patients with sEOAD (n = 110), late-onset AD (LOAD, n = 89), young controls (YC, n = 50), and older controls (OC, n = 25). All AD patients fulfilled the diagnostic criteria based on biomarker evidence. Familial EOAD patients or non-AD dementia patients were excluded. Single molecule array technology was used to measure fluid biomarkers, including cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ) 40, Aβ42, phosphorylated tau (P-tau) 181, total tau (T-tau), serum neurofilament light chain and glial fibrillary acidic protein (GFAP). Patients with sEOAD exhibited more severe executive function impairment and bilateral precuneus atrophy (P < 0.05, family-wise error corrected) than patients with LOAD. Patients with sEOAD showed elevated CSF and plasma P-tau181 levels (154.0 ± 81.2 pg/mL, P = 0.002; and 6.1 ± 2.3 pg/mL, P = 0.046). Moreover, precuneus atrophy was significantly correlated with serum GFAP levels in sEOAD (P < 0.001). Serum GFAP levels (area under the curve (AUC) = 96.0%, cutoff value = 154.3 pg/mL) displayed excellent diagnostic value in distinguishing sEOAD patients from the control group. These preliminary findings highlight the crucial role of tau protein phosphorylation in the pathogenesis and progression of sEOAD.

Demographic and Clinical Characteristics Associated With Serum GFAP Levels in an Ethnically Diverse Cohort.

Elevations in circulating glial fibrillary acidic protein (GFAP), a putative marker of reactive astrocytosis, have been found to associate with cognitive decline and dementia status. Further validation in diverse cohorts and evaluation of potential health disparities are necessary for broader generalization. The goal of this study was to examine the associations between demographics, cardiovascular risk factors, and APOE ε4 status with serum GFAP levels among Mexican American and non-Hispanic White older adults across the continuum from cognitively unimpaired to Alzheimer disease dementia. Serum GFAP levels were assayed using a Simoa HD-1 analyzer in older adults enrolled in the observational Texas Alzheimer Research and Care Consortium. Associations between demographic and clinical characteristics with serum GFAP levels were evaluated using linear regression. The diagnostic accuracy of serum GFAP was further examined using area under the receiver operating characteristic curves (AUROC) in univariate and adjusted models, and optimal cut points were derived using the maximum Kolmogorov-Smirnov metric. All models were also stratified by ethnicity and disease stage. A total of 1,156 Mexican American and 587 non-Hispanic White participants were included (mean age = 68 years, standard deviation = 10; 65% female). Older age (β = 0.562 (95% CI 0.515-0.609), p < 0.001), apolipoprotein ε4 status (β = 0.139 (95% CI 0.092-0.186), p < 0.001), and cognitive impairment (β = 0.150 (95% CI 0.103-0.197), p < 0.001) were positively associated with serum GFAP. By contrast, higher body mass index (β = -0.181 (95% CI -0.228 to -0.134), p < 0.001), diabetes (β = -0.065 (95% CI -0.112 to -0.018), p < 0.001), and tobacco use (β = -0.059 (95% CI -0.106 to -0.012), p < 0.001) were inversely associated with serum GFAP. AUROC values were generally comparable across ethnicities and model fit improved with inclusion of additional covariates. However, optimal cut-off values were consistently lower in Mexican Americans relative to non-Hispanic White participants. The study results highlight the importance of understanding the role of broader demographic and clinical factors on circulating GFAP levels within diverse cohorts to enhance precision across clinical, research, and community settings.

Serum levels of 25-OH vitamin D levels predict cognitive impairments among acute coronary syndrome patients.

The cognitive impairment after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) has become a crucial clinical concern that cannot be ignored. However, studies on the early warning factors of cognitive impairment after PCI are still insufficient. This study reviewed the postoperative cognitive function of 284 patients who underwent PCI in our hospital from June 2019 to June 2022. During the 21-day follow-up, all participants included in the analysis were divided into the cognitive impairment (CI) group (n = 82) and the noncognitive impairment (NCI) group (n = 186) according to their Montreal cognitive assessment (MoCA) scale. Participants' serum 25(OH)D3 levels on admission and serum neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S100β levels were measured 21 days after surgery. Age more than 65 years, hypertension, operation time longer than 60 min, left ventricular ejection fraction less than 50% and serum 25(OH)D3 less than 31.41 ng/ml were the risk factors for cognitive dysfunction in ACS patients 21 days after PCI. Serum levels of 25(OH)D3, NSE, S100β and GFAP were significantly higher in patients with cognitive impairment than in patients without cognitive impairment. Postoperative serum NSE, S100β and GFAP levels were significantly negatively correlated with serum 25(OH)D3 levels at admission. The serum 25(OH)D3 level is a risk factor and predictor of cognitive impairment in patients with ACS after PCI.

Pre-Analytical Variables Influencing Stability of Blood-Based Biomarkers of Neuropathology.

Sample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology. To evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions. We collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4∘C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4∘C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-β 40 (Aβ40), amyloid-β 42 (Aβ42), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181). We found that Aβ40 and Aβ42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p < 0.0001). Nevertheless, serum Aβ42/40 ratio remained stable with a processing delay up to 48 h while plasma Aβ42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma. These results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies.

Serum neurofilament and glial fibrillary acidic protein in idiopathic and seropositive transverse myelitis

BackgroundSerum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS) demyelinating diseases. However, the clinical significance of NfL and GFAP in idiopathic transverse myelitis (iTM), an inflammatory spinal cord disease with unknown underlying causes, remains unclear. This study aimed to investigate NfL and GFAP levels in iTM and their association with the clinical parameters compared with those in TM with disease-specific antibodies such as anti-aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies (sTM). MethodsWe collected serum and clinical data of 365 patients with CNS inflammatory diseases from 12 hospitals. The serum NfL and GFAP levels were measured in patients with iTM (n = 37) and sTM (n = 39) using ultrasensitive single-molecule array assays. Regression analysis was performed to investigate the associations between serum levels of NfL and GFAP and the clinical parameters such as higher EDSS scores (EDSS ≥ 4.0). ResultsMean NfL levels were not significantly different between iTM (50.29 pg/ml) and sTM (63.18 pg/ml) (p = 0.824). GFAP levels were significantly lower in iTM (112.34 pg/ml) than in sTM (3814.20 pg/ml) (p = 0.006). NfL levels correlated with expanded disability status scale (EDSS) scores in sTM (p = 0.001) but not in iTM (p = 0.824). Disease duration also correlated with higher EDSS scores in sTM (p = 0.017). ConclusionNfL levels and disease duration correlated with EDSS scores in sTM, and GFAP levels could be a promising biomarker to differentiate iTM from sTM.

Association between serum neurofilament light chain levels and sleep disorders in patients with Parkinson’s disease

ObjectivesThis study aimed to investigate the levels of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in patients with Parkinson's disease (PD) and PD patients with sleep disorders (PD-SD), as well as the relationship between these proteins and sleep disorders in PD patients. MethodsA total of 96 PD patients and 38 healthy controls (HC) were included in this study, of which 70 PD patients experienced sleep disorders. Both motor symptoms and sleep conditions were assessed in all PD patients. The ultrasensitive single molecule array (SIMOA) technique was used to quantify NFL and GFAP in the serum. All data were statistically analyzed using SPSS 23.0. ResultsSerum NFL and GFAP levels were significantly higher in PD patients than in HC. Similarly, PD-SD patients exhibited higher levels of these two proteins than PD patients without sleep disorders (PD-NSD). In addition, both serum GFAP and NFL were significantly associated with sleep-related scales in PD patients. After covariate-adjusted binary logistic regression analysis, NFL remained statistically significant in PD patients with or without sleep disorders, unlike GFAP. ConclusionsOur findings substantiate that serum NFL and GFAP levels are elevated in PD and PD-SD, suggesting neurological axon damage in PD patients, which may be more severe in PD-SD than in PD-NSD. These findings may affect disease diagnosis and provide the foothold for future studies on the underlying mechanisms.

Changes and significance of serum ubiquitin carboxyl-terminal hydrolase L1 and glial fibrillary acidic protein in patients with glioma

Brain gliomas are malignant tumors with high postoperative recurrence rates. Early prediction of prognosis using specific indicators is of great significance. To assess changes in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) levels in patients with glioma pre-and postoperatively. Between June 2018 and June 2021, 91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group. Sixty healthy volunteers were included in the control group. Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery. UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery. The patients were followed-up until February 2022. Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels, which could assist in predicting postoperative glioma recurrence. UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy (P < 0.05). However, UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery (P < 0.05). There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex, age, pathological type, tumor location, or number of lesions (P > 0.05). Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with grade III-IV tumors (P < 0.05). Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter ≤ 5 cm than in those with diameter > 5 cm, in which the differences were statistically significant (P < 0.05). Glioma recurred in 22 patients. The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group (P < 0.05). Receiver operating characteristic curves were plotted. The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775, respectively. However, the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels. UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.

Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients.

Identification of reliable and accessible biomarkers to characterize ischemic stroke patients' prognosis remains a clinical challenge. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are markers of brain injury, detectable in blood by high-sensitive technologies. Our aim was to measure serum NfL and GFAP after stroke, and to evaluate their correlation with functional outcome and the scores in rehabilitation scales at 3-month follow-up. Stroke patients were prospectively enrolled in a longitudinal observational study within 24 hours from symptom onset (D1) and monitored after 7 (D7), 30 ± 3 (M1) and 90 ± 5 (M3) days. At each time-point serum NfL and GFAP levels were measured by Single Molecule Array and correlated with National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Trunk Control Test (TCT), Functional Ambulation Classification (FAC) and Functional Independence Measure (FIM) scores. Serum NfL and GFAP showed different temporal profiles: NfL increased after stroke with a peak value at D7; GFAP showed an earlier peak at D1. NfL and GFAP concentrations correlated with clinical/rehabilitation outcomes both longitudinally and prospectively. Multivariate analysis revealed that NfL-D7 and GFAP-D1 were independent predictors of 3-month NIHSS, TCT, FAC and FIM scores, with NfL being the biomarker with the best predictive performance.

Development of an ultrasensitive microfluidic assay for the analysis of Glial fibrillary acidic protein (GFAP) in blood.

Introduction: A rapid and reliable detection of glial fibrillary acidic protein (GFAP) in biological samples could assist in the diagnostic evaluation of neurodegenerative disorders. Sensitive assays applicable in the routine setting are needed to validate the existing GFAP tests. This study aimed to develop a highly sensitive and clinically applicable microfluidic immunoassay for the measurement of GFAP in blood. Methods: A microfluidic GFAP assay was developed and validated regarding its performance. Subsequently, serum and cerebrospinal fluid (CSF) of Alzheimer's disease (AD), Multiple Sclerosis (MS) and control patients were analyzed with the established assay, and levels were compared to the commercial GFAP Simoa discovery kit. Results: The developed GFAP assay showed a good performance with a recovery of 85% of spiked GFAP in serum and assay variations below 15%. The established assay was highly sensitive with a calculated lower limit of quantification and detection of 7.21pg/mL and 2.37pg/mL, respectively. GFAP levels were significantly increased in AD compared to control patients with advanced age (p = 0.002). However, GFAP levels revealed no significant increase in MS compared to control patients in the same age range (p = 0.140). Furthermore, serum GFAP levels evaluated with the novel microfluidic assay strongly correlated with Simoa concentrations (r = 0.88 (95% CI: 0.81-0.93), p < 0.0001). Conclusion: We successfully developed a sensitive and easy-to-use microfluidic assay to measure GFAP in blood. Furthermore, we could confirm previous findings of elevated GFAP levels in AD by applying the assay in a cohort of clinically characterized patients.

Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726, p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.

Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study.

Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes. A case-control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measuredby Simoa. Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAPwere significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2years of follow-up (139.1 ± 52.5pg/mL vs. 100.2 ± 54.6pg/mL; p = 0.04). GFAP could be a useful serumbiomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.

RTMS ameliorates depression/anxiety-like behaviors in experimental autoimmune encephalitis by inhibiting neurotoxic reactive astrocytes

One third of patients with multiple sclerosis (MS) suffered from depressive symptoms. The pathogenesis of depression in MS patients has been related to innate immune activation in certain regions of the brain such as hippocampus. However, pharmacotherapy lacks sufficient evidence for beneficial effects on depression in MS patients, urging for a novel treatment modality for this mental disorder. Treatment effects of rTMS on depression/anxiety-like behaviors in mice with experimental autoimmune encephalomyelitis (EAE) were assessed by behavioral tests. The role of innate immune response was examined by RNA sequencing, quantitative RT-PCR, and immunofluorescence techniques. Depressive symptom severity and astroglial activation in patients with MS were assessed by Beck Depression Inventory and serum glial fibrillary acidic protein (GFAP), respectively. EAE mice displayed depression/anxiety-like behaviors, which were ameliorated by rTMS. Transcriptome and gene-specific expression analysis of the hippocampus showed significant reduction in transcript levels associated with neurotoxic reactive astrocytes in EAE mice after rTMS treatment. This was confirmed by immunofluorescence studies. Complement component 3d, a marker of neurotoxic reactive astrocytes, was highly expressed in EAE hippocampus, but was reduced to a basal level after rTMS treatment. In patients with MS, astroglial activation, indicated by serum GFAP levels, was significantly elevated in those with moderate or major depressive symptoms. These findings support that the suppression of neurotoxic reactive astrocytes might be a potential target for treatment of depression in patients with MS, and suggest the potential of using rTMS as a potential therapeutic treatment for this disorder.

Serum ubiquitin C-terminal hydrolase-L1, glial fibrillary acidic protein, and neurofilament light chain are good entry points and biomarker candidates for neurosyphilis diagnosis among patients without HIV to avoid lumbar puncture.

Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed. This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without HIV and to evaluate their diagnostic performance in neurosyphilis compared with CSF. Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cut-off levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively. To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson's disease.

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.

Association of serum neurofilament light chain and glial fibrillary acidic protein levels with cognitive decline in Parkinson’s disease

ObjectivesTo investigate whether serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels are associated with motor and cognitive function in Parkinson’s disease (PD). MethodsThis cross-sectional study recruited 140 participants, including 103 PD patients and 37 healthy controls (HC). Serum NfL and GFAP levels were measured using the ultrasensitive single-molecule array (Simoa) technique. Motor and cognitive function were evaluated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) and Beijing version of the Montreal Cognitive Assessment (MoCA). Spearman’s correlation analyses were used to determine the correlation between serum NfL and GFAP levels and clinical features in PD patients. Binary logistic regression analysis was used to assess the association between serum biomarkers and cognitive impairment in PD patients. ResultsWe observed significantly higher serum NfL and GFAP levels in PD patients than in HC (p < 0.001). Serum NfL and GFAP levels were negatively correlated with MoCA scores (NfL: r = − 0.472, p < 0.001; r = 0.395, p < 0.001) and multiple cognitive domains and showed no correlation with motor symptom severity after adjusting for age and sex. Binary logistic regression analysis showed that the serum NfL and GFAP levels were independent contributors to PD with dementia (p < 0.05). ConclusionsBoth serum NfL and GFAP levels correlated with cognitive impairment, but not motor symptoms, in PD patients. Serum NfL and GFAP levels can serve as biomarkers for PD patients at risk of cognitive decline.

Serum Markers of Neuronal Damage and Astrocyte Activity in Patients with Chronic Epilepsy: Elevated Levels of Glial Fibrillary Acidic Protein

Objectives. Blood-brain barrier (BBB) dysfunction is one of the key pathogenic mechanisms in the development of epilepsy. There is therefore an increasing need to identify BBB biomarkers as these will have prognostic and therapeutic implications. The purpose of this study was to assess the levels of the BBB permeability markers, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), S100B, and furin in patients with stable epilepsy compared with the levels in healthy controls. Materials and Methods. This cross-sectional study included 119 epilepsy patients and 80 healthy controls. Circulating levels of GFAP, NSE, S100B, and furin were measured and questionnaires regarding epilepsy, use of drugs, and comorbidities were completed by all participants. Results. GFAP levels were higher in epilepsy patients after adjustment for potential confounders (sex, age, and BMI) in linear regression ( p = 0.042 ). No significant differences were found in levels of S100B, NSE, or furin. None of the markers were significantly associated with epilepsy duration, seizure type or severity, or seizures in the preceding six months. The majority of the patients (79.7%) did not report seizures within the last 6 months. Conclusion. Our main finding is elevated serum levels of GFAP in epilepsy patients. The results may suggest the presence of astrocyte activation in our patient population with stable epilepsy. Future prospective studies focusing on the longitudinal relationship between epilepsy debut, seizures, and time of blood sampling for BBB markers, also within CSF, could provide valuable knowledge including regarding novel treatment options. The study registration number is 2011/1096, 2018/1437.

Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study.

Autism spectrum disorder (ASD) is one of the most common neurodevelopment disorders, characterized by a multifactorial etiology based on the interaction of genetic and environmental factors. Recent evidence supports the neurobiological hypothesis based on neuroinflammation theory. To date, there are no sufficiently validated diagnostic and prognostic biomarkers for ASD. Therefore, we decided to investigate the potential diagnostic role for ASD of two biomarkers well known for other neurological inflammatory conditions: the glial fibrillary acidic protein (GFAP) and the neurofilament (Nfl). Nfl and GFAP serum levels were analyzed using SiMoA technology in a group of ASD patients and in a healthy control group (CTRS), age- and gender-matched. Then we investigated the distribution, frequency, and correlation between serum Nfl and GFAP levels and clinical data among the ASD group. The comparison of Nfl and GFAP serum levels between ASD children and the control group showed a mean value of these two markers significantly higher in the ASD group (sNfL mean value ASD pt 6.86 pg/mL median value ASD pt 5.7 pg/mL; mean value CTRS 3.55 pg/mL; median value CTRS 3.1 pg; GFAP mean value ASD pt 205.7 pg/mL median value ASD pt 155.4 pg/mL; mean value CTRS 77.12 pg/mL; median value CTRS 63.94 pg/mL). Interestingly, we also found a statistically significant positive correlation between GFAP levels and hyperactivity symptoms (p-value <0.001). Further investigations using larger groups are necessary to confirm our data and to verify in more depth the potential correlation between these biomarkers and ASD clinical features, such as the severity of the core symptoms, the presence of associated symptoms, and/or the evaluation of a therapeutic intervention. However, these data not only might shed a light on the neurobiology of ASD, supporting the neuroinflammation and neurodegeneration hypothesis, but they also might support the use of these biomarkers in the early diagnosis of ASD, to longitudinally monitor the disease activity, and even more as future prognostic biomarkers.

The Correlation of Glial Fibrillary Acid Protein Level to Cognitive Function Outcome in Acute Lacunar Ischemic Stroke Patient

ABSTRACT :&#x0D; Introduction : Glial fibrillary acidic protein (GFAP) is a filamentous protein found in central nervous system astrocytes. Increased serum GFAP levels are caused by the process of astrogliosis after ischemic stroke and are associated with multisynaptic disorders so that they are at risk of causing cognitive disorders.&#x0D; Objective: To analyze the correlation between GFAP levels and cognitive function output in acute lacunar ischemic stroke patients.&#x0D; Research Methods : Analytical observational with prospective cohort approach. The subjects of this study were Acute lacunar ischemic stroke patients with mild to moderate NIHSS scores. Serum GFAP levels were taken at the onset of 48-72 hours of stroke. Cognitive function was measured using the Indonesian version of MoCA (MoCA Ina) test on the seventh and thirtieth day. Bivariate and multivariate analyzes were performed to assess the correlation between GFAP levels, cognitive functions and the confounding factors.&#x0D; Results: There was a significant correlation between GFAP levels and the MoCA Ina scores on the seventh day (r= -0.32, p=0.044), the thirtieth day (r= -0.398, p=0.011), and improvement in MoCA Ina scores (r= -0.342, p = 0.031). There was a significant correlation between GFAP levels on the executive domain on the seventh day (p= 0.01) and thirtieth day (p= 0.005), visuospatial on seventh day (p= 0.004) and thirtieth day (p= 0.016), language on the thirtieth day (p = 0.005), and memory on thirtieth day (p= 0.001). There was no significant correlation between GFAP levels and improvements in attentional, memory, language, visuospatial, and executive domains.&#x0D; Conclusion: There was a significant correlation between GFAP levels and MoCA Ina scores on the seventh, thirtieth day and the improvement of MoCA Ina scores. There was a significant correlation between GFAP levels with the executive, visuospatial, language, and memory domains.&#x0D; Keywords: cognitive, GFAP, lacunar ischemic stroke, MoCA Ina

Elevated serum levels of glial fibrillary acidic protein are associated with covert hepatic encephalopathy in patients with cirrhosis

Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. Astrocyte swelling is a major component of hepatic encephalopathy. Thus, we hypothesised that glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, might facilitate early diagnosis and management. This study aimed to investigate the utility of serum GFAP (sGFAP) levels as a biomarker of CHE. In this bicentric study, 135 patients with cirrhosis, 21 patients with ongoing harmful alcohol use and cirrhosis, and 15 healthy controls were recruited. CHE was diagnosed using psychometric hepatic encephalopathy score. sGFAP levels were measured using a highly sensitive single-molecule array (SiMoA) immunoassay. In total, 50 (37%) people presented with CHE at study inclusion. Participants with CHE displayed significantly higher sGFAP levels than those without CHE (median sGFAP, 163pg/ml [IQR 136; 268] vs. 106pg/ml [IQR 75; 153]; p <0.001) or healthy controls (p <0.001). sGFAP correlated with results in psychometric hepatic encephalopathy score (Spearman's ρ=-0.326, p <0.001), model for end-stage liver disease score (Spearman's ρ= 0.253, p= 0.003), ammonia (Spearman's ρ= 0.453, p= 0.002), and IL-6 serum levels (Spearman's ρ= 0.323, p= 0.006). Additionally, sGFAP levels were independently associated with the presence of CHE in multivariable logistic regression analysis (odds ratio 1.009; 95% CI 1.004-1.015; p <0.001). sGFAP levels did not differ between patients with alcohol-related cirrhosis vs. patients with non-alcohol-related cirrhosis or between patients with ongoing alcohol use vs. patients with discontinued alcohol use.Conclusions: sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker. Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. In this study, we were able to demonstrate that sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.