Serum Glial Fibrillary Acidic Protein Levels Research Articles

Serum Glial Fibrillary Acidic Protein in Detecting Intracranial Injuries Following Minor Head Trauma; a Systematic Review and Meta-Analysis.

Developing novel diagnostic and screening tools for exploring intracranial injuries following minor head trauma is a necessity. This study aimed to evaluate the diagnostic value of serum glial fibrillary acidic protein (GFAP) in detecting intracranial injuries following minor head trauma. An extensive search was performed in Medline, Embase, Scopus, and Web of Science databases up to the end of April 2022. Human observational studies were chosen, regardless of sex and ethnicity of their participants. Pediatrics studies, report of diagnostic value of GFAP combined with other biomarkers (without reporting the GFAP alone), articles including patients with all trauma severity, defining minor head trauma without intracranial lesions as the outcome of the study, not reporting sensitivity/specificity or any other values essential for computation of true positive, true negative, false positive and false-negative, being performed in the prehospital setting, assessing the prognostic value of GFAP, duplicated reports, preclinical studies, retracted articles, and review papers were excluded. The result was provided as pooled sensitivity, specificity, diagnostic score and diagnostic odds ratio, and area under the summary receiver operating characteristic (SROC) curve with a 95% confidence interval (95% CI). Eventually, 11 related articles were introduced into the meta-analysis. The pooled analysis implies that the area under the SROC curve for serum GFAP level in minor traumatic brain injuries (TBI) was 0.75 (95% CI: 0.71 to 0.78). Sensitivity and specificity of this biomarker in below 100 pg/ml cut-off were 0.83 (95% CI: 0.78 to 0.89) and 0.39 (95% CI: 0.24 to 0.53), respectively. The diagnostic score and diagnostic odds ratio of GFAP in detection of minor TBI were 1.13 (95% CI: 0.53 to 1.74) and 3.11 (95% CI: 1.69 to 5.72), respectively. The level of evidence for the presented results were moderate. The present study's findings demonstrate that serum GFAP can detect intracranial lesions in mild TBI patients. The optimum cut-off of GFAP in detection of TBI was below 100 pg/ml. As a result, implementing serum GFAP may be beneficial in mild TBI diagnosis for preventing unnecessary computed tomography (CT) scans and their related side effects.

Clinical utility of serum glial fibrillary acidic protein in glial neoplasm.

Glial fibrillary acidic protein (GFAP) is a member of the cytoskeletal protein family and is widely expressed in astroglial and neural stem cells, also in glial tumors such as astrocytoma and Glioblastoma (GBM). Increased GFAP expression and disruption of the blood-brain barrier are the characteristic features of GBM. Higher serum GFAP levels can help differentiate GBM from GBM mimics (such as primary central nervous system lymphoma, metastasis, or demyelinating lesions). This prospective study was carried out in a tertiary care center in the department of neurosurgery on newly diagnosed glioma patients who underwent surgery from January 2018 to July 2019, excluded patients with history of the previous surgery for glioma, traumatic brain injury, and ischemic or hemorrhagic stroke. The blood sample was obtained at admission before undergoing invasive procedure. Pathological examination of the tumor biopsy sample was carried out using classical hematoxylin-eosin and immunohistochemical staining. All statistical analyses were performed using SPSS version 24.0. The mean preoperative tumor volume was 40 cm3 (range 17.19-65.57 cm3; standard deviation [SD] = 9.99 cm3) which showed 98.25% mean reduction in volume postsurgery (mean tumor volume = 0.7 cm3; SD = 0.19 cm3). Preoperative serum GFAP measurements show higher levels (spearman's rho coefficient = 0.610 with P = 0.000) with increasing grade of tumor. GFAP levels also demonstrated higher value with increasing preoperative tumor volume. Increasing serum GFAP levels in the preoperative period correlate with higher tumor grade, especially grade III and grade IV tumors. The serum GFAP levels showed relation to tumor volume, both before and after surgery.

Trajectory of Serum Levels of Glial Fibrillary Acidic Protein Within Four Weeks Post-Injury Is Related to Neurological Recovery During the Transition from Acute to Chronic Spinal Cord Injury.

The use of biomarkers in spinal cord injury (SCI) research has evolved rapidly in recent years whereby most studies focused on the acute post-injury phase. Since SCI is characterized by persisting neurological impairments, the question arises whether blood biomarkers remain altered during the subacute post-injury time. Sample collection in the subacute phase might provide a better insight in the ongoing SCI specific molecular mechanism with fewer confounding factors compared with the acute phase where, amongst other complications, individuals receive a substantial amount of medication. This study aimed to determine if the temporal dynamics of serum biomarkers of neurodegeneration differ between individuals depending on their extent of neurological recovery in the transition phase between acute and chronic SCI. We performed a secondary analysis of biomarkers in patients with SCI (n = 41) who were treated at a level I trauma center in Germany. Patients with cervical or thoracic SCI regardless of injury severity were included. Blood samples were collected in the acute phase (1-4 days post-injury), and after 30 and 120 days post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were determined for each time-point of sample collection using R-Plex Assays (Meso Scale Discovery). Linear mixed models were used to evaluate the trajectory of GFAP and NfL over time. Fixed effects of time, neurological recovery, and injury severity, along with the recovery-by-time interaction, were included in models with random slopes and intercepts. GFAP levels increase during the first days after SCI and decrease in subacute to chronic stages. Notably, the trajectory of GFAP over time is significantly associated with the extent of neurological recovery during the transition from acute to chronic SCI with a steeper decline in individuals who recovered better. Serum levels of NfL continue to rise significantly until Day 30 followed by a decrease afterwards, independent of neurological recovery. The trajectory of serum GFAP levels qualifies as a prognostic biomarker for neurological recovery, and facilitates monitoring of disease progression in the sub-acute post-injury phase.

A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.

The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of biofluid-based biomarkers. To investigate the diagnostic potential of a combination of novel biomarkers in cerebrospinal fluid (CSF) and blood. We included 135 patients from the Center for Memory Disturbances, University of Perugia, with the diagnoses FTD (n = 37), mild cognitive impairment due to Alzheimer's disease (MCI-AD, n = 47), Lewy body dementia (PDD/DLB, n = 22), and cognitively unimpaired patients as controls (OND, n = 29). Biomarker levels of neuronal pentraxin-2 (NPTX2), neuronal pentraxin receptor, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured in CSF, as well as NfL and GFAP in serum. We assessed biomarker differences by analysis of covariance and generalized linear models (GLM). We performed receiver operating characteristics analyses and Spearman correlation to determine biomarker associations. CSF NPTX2 and serum GFAP levels varied most between diagnostic groups. The combination of CSF NPTX2, serum NfL and serum GFAP differentiated FTD from the other groups with good accuracy (FTD versus MCI-AD: area under the curve (AUC) [95% CI] = 0.89 [0.81-0.96]; FTD versus PDD/DLB: AUC = 0.82 [0.71-0.93]; FTD versus OND: AUC = 0.80 [0.70-0.91]). CSF NPTX2 and serum GFAP correlated positively only in PDD/DLB (ρ= 0.56, p < 0.05). NPTX2 and serum NfL did not correlate in any of the diagnostic groups. Serum GFAP and serum NfL correlated positively in all groups (ρ= 0.47-0.74, p < 0.05). We show the combined potential of CSF NPTX2, serum NfL, and serum GFAP to differentiate FTD from other neurodegenerative disorders.

Association of Serum GFAP with Functional and Neurocognitive Outcome in Sporadic Small Vessel Disease.

Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pathological analyses in CSVD revealed a high density of GFAP-immunoreactive fibrillary astrocytic processes in the periventricular white matter and clusters of CHI3L1-immunoreactive astrocytes in the basal ganglia and thalamus. Thus, besides NfL, serum GFAP is a highly promising fluid biomarker of sporadic CSVD, because it does not only correlate with the clinical severity but also correlates with the cognitive function in patients.

Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels

Background: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs). Objective: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS). Methods: We measured NfL, GFAP, and MMPs in blood samples from 96 patients with CIS from the MinoCIS study and compared biomarkers with clinical and radiologic characteristics and outcome. Results: At baseline, NfL levels correlated with T2 lesion load and number of gadolinium-enhancing lesions. Baseline NfL levels predicted conversion into CDMS at month 6. GFAP levels at baseline were correlated with T2 lesion volume. Minocycline treatment significantly increased NfL levels at 3 months but not at 6 months, and decreased GFAP levels at month 6. Minocycline decreased MMP-7 concentrations at month 1. Discussion: Blood NfL levels are associated with measures of disease activity in CIS and have prognostic value. Minocycline increased NfL levels at month 3, but reduced GFAP and MMP-7 levels.

Serum Levels of Glial Fibrillary Acidic Protein Association with Cognitive Impairment and Type 2 Diabetes

Peripheral biomarkers associated with neurocognitive disorders (NCD) have been evaluated in an attempt to improve diagnosis and early detection and potentially even prevent them. Along with increasing age, type 2 diabetes (T2D) increases the risk of central nervous system disorders and cognitive impairment due to the loss of synaptic function. Central damage triggers an astroglial response, increasing the expression of glial fibrillary acidic protein (GFAP), which can be found peripherally when the blood-brain barrier is compromised. To evaluate the value of GFAP as a peripheral biomarker of central dysfunction. Serum levels of GFAP were compared between cases of NCD (n=69) and age-matched controls (n=69), analyzing the influence of diabetes as contributing factor. We found higher levels of serum GFAP in subjects with NCD compared with the control group (p <0.0001). The receiver operating characteristic (ROC) curve using the GFAP levels showed 65.22% sensitivity and 71.01% specificity (AUC=0.7608), indicating good performance in the classification of controls and NCD patients. Logistic regression indicated a positive predictive power of 67.50% considering T2D status; adding GFAP levels, the predictive power rises to 71.93%. GFAP levels and T2D could be considered good predictors of NCD risk. Our findings open the possibility that peripheral GFAP could be used as an objective measurement related, under certain conditions, to central damage; thereby serving as a follow-up marker to refer diabetic patients for appropriate neurological evaluation, which could offer a low cost, minimally invasive strategy to improve the assessment of cognitive affectation and subsequent treatment.

Plasma biomarkers of brain injury in COVID-19 patients with neurological symptoms

ObjectiveNeurological symptoms (NS) were often reported in COVID-19 infection. We examined the plasma levels of glial fibrillary acidic protein (GFAP) and S100B together, as brain injury biomarkers, in relation to persistent NS in a cohort of patients with COVID-19 during the acute phase of the disease. MethodsA total of 20 healthy controls and 58 patients with confirmed COVID-19 were enrolled in this prospective study. Serum GFAP and S100B levels were measured by using enzymle linked immunoassay method from blood samples. ResultsSerum GFAP levels were found to be significantly higher in the severe group than in the controls (p = 0.007). However, serum S100B levels were similar between control and disease groups (p > 0.05). No significant results for GFAP and S100B were obtained between the disease groups depending on whether the sampling time was below or above 5 days (p > 0.05). We did not find a correlation between serum GFAP and S100B levels and the presence of NS (p > 0.05). However, serum S100B levels were slightly higher in patients with multiple NS than in those with a single symptom (p = 0.044). ConclusionsElevated GFAP was associated with disease severity but not with NS in COVID-19 patients. Whereas, high serum S100B was associated with the multipl NS in these patients. Our data suggest that GFAP and S100B may be of limited value currently in order to represent the neuronal damage, though serving a basis for the future work.

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure.

AimsCognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF.Methods and resultsUsing bead‐based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters‐HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty‐six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end‐systolic volume index (T = 3.4; P = 0.004). NT‐proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025).ConclusionsSerum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

Circulating neurofilament is linked with morbid obesity, renal function, and brain density

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion

ObjectiveReactive astrogliosis is a hallmark of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) but differences between the diseases and time course are unclear. Here, we used serum levels of the...

Analysis of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 in Postmortem Serum and Cerebrospinal Fluid in Traumatic Cerebral Deaths

Objective: There is a growing body of research aimed at identifying biological markers that could indicate traumatic cerebral deaths such as traumatic brain damage in the postmortem period. In the event of astrocytic and neuronal injury, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are released into cerebrospinal fluid and blood. In the postmortem identification of traumatic brain injury, the present research explores the ability of GFAP and UCH-L1.&#x0D; Methods: Cerebrospinal fluid and blood samples were obtained from medicolegal autopsies, 17 cases with severe head trauma, 9 cases with the non-lethal head trauma group and 18 control cases. UCH-L1 and GFAP levels in postmortem cerebrospinal fluid and serum were determined&#x0D; from an enzyme-linked immunosorbent assay (ELISA).&#x0D; Results: GFAP level in cerebrospinal fluid and serum was 2.68±0.67 ng/ml and 0.79±0.92 ng/ml in the lethal head trauma group, 2.74±0.64 ng/ml and 1.05±0.68 ng/ml the non-lethal head trauma group and 2.49±0.55 ng/ml and 1.05±0.89 ng/ml in the control group, respectively.&#x0D; UCH-L1 level in cerebrospinal fluid and serum was 3.02±0.68 ng/ml and 2.69±0.77 ng/ml in the lethal head trauma group, 3.34±0.70 ng/ml and 2.59±0.65 ng/ml the non-lethal head trauma group and 3.28±0.33 ng/ml and 2.74±0.34 ng/ml in the control group, respectively. Elevated cerebrospinal fluid and serum UCH-L1 and GFAP levels were observed in all cases, although absence of statistically significant difference between the trauma and control groups (p&gt;0.05).&#x0D; Conclusion: Further studies are needed to assess whether postmortem serum and CSF GFAP and UCH-L1 concentrations increase regardless of the cause of death.

Investigation of Early Diagnostic Value of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase Blood Levels in Minor Head Trauma in Turkey.

The aim was to investigate the early diagnostic value of serum glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels in adults with minor head trauma (MHT) and whether it could be an alternative diagnostic method to computed tomography (CT). This is the first study with the combination of GFAP and UCH-L1 in the first 3 hours of MHT. The study comprised 88 patients, 60 patients and 28 controls, who were evaluated as having MHT, were admitted to the emergency department of our hospital within the first 3 hours of the trauma and met the inclusion criteria. CT was performed on all patients. Serum GFAP and UCH-L1 levels were measured within the first 3 hours of the trauma. The median serum GFAP level was 1.07 ng/mL in the group with pathology on CT and 0.42 ng/mL in the group with no pathology on CT. The median serum UCH-L1 level was 0.40 ng/mL in the group with pathology on CT and 0.39 ng/mL in the group with no pathology on CT. A statistically significant difference was found between the serum GFAP levels of the CT (+) group and the CT (-) group (p = 0.021). GFAP levels were compared according to the CT (+) and CT (-) groups with a cutoff value of ≥ 1.56 ng/mL for GFAP, which had 50% sensitivity and 97.5% specificity. This was statistically significant (p = 0.008). It was found that the UCH-L1 level of the control group was lower than the UCH-L1 levels of the CT (+) and CT (-) groups, and this difference was found to be statistically significant (p = 0.003 and p = 0.018, respectively). GFAP was found to be more specific than UCH-L1 in demonstrating the presence of intracranial pathology in patients with head trauma who were admitted to the emergency department in the first 3 hours after trauma.

Glial Fibrillary Acidic Protein (GFAP): Neuroinflammation Biomarker in Acute Ischemic Stroke.

IntroductionBlockage of the cerebral arteries due to thrombosis and embolism resulting in decreased blood flow to the brain, reduced oxygen supply to the brain, resulting in neuronal damage and causes astrocyte cells to secrete glial fibrillary acidic protein (GFAP). The objective of this study was to determine the correlation between GFAP levels serum and clinical outcome in patients with acute ischemic stroke.MethodsThis was observational with a cross-sectional design on acute ischemic stroke patients confirmed by CT scans and divided into large vessel occlusion and small-vessel occlusion. Clinical outcome was measured using the National Institutional Health Stroke Scale (NIHSS) tool. Statistical analysis uses Spearman’s rank correlation test and Mann Whitney’s test, significant if p < 0.05.ResultsAfter collecting 33 research subjects, we found 16 people with large vessel occlusion and 17 people with small vessel occlusion. Serum GFAP levels were 0.2–1.9 ng/mL, 9.1% with a mild neurological deficit, 45.45% were moderate neurological deficits, and 45.45% were severe neurological deficits. There was a significant positive correlation (r = 0.522; p = 0.002) between serum GFAP levels and the degree of neurological deficit in ischemic stroke patients. There was a statistically significant difference between serum GFAP levels in ischemic stroke patients with CT scan results of large artery occlusion compared to small artery occlusion (0.7 vs 0.4ng/mL; p = 0.001).ConclusionThere was a positive correlation between GFAP level serum and NIHSS score on acute ischemic stroke. The higher the value of GFAP serum level, the higher the value for NIHSS and correlated with stroke severity and the extent of brain damage in ischemic stroke patients.

Blood markers of neuronal/axonal and glial injury for clinical progression in a predominately Hispanic cohort: The Texas Alzheimer’s Research and Care Consortium

AbstractBackgroundThe clinical translation of biofluid markers for Alzheimer’s disease and related dementias (ADRDs) requires validation in diverse cohorts. The goal of the study was to evaluate if blood biomarkers of neuronal/axonal and glial injury predict cognitive decline and clinical disease progression in a predominately Hispanic cohort from the Texas Alzheimer’s Research and Care Consortium.MethodParticipants included 745 Hispanic and 274 non‐Hispanic white participants, aged 55‐89 years, who annually completed cognitive assessments, the Clinical Dementia Rating scale (CDR), and dementia consensus reviews. Serum from the baseline examination was assayed to quantify levels of total tau (t‐tau), neurofilament light (NFL), ubiquitin carboxyl‐terminal hydrolase LI (UCHLI), and glial fibrillary acidic protein (GFAP) using the Simoa Neurology 4‐Plex Kit (Quanterix), as well as soluble CD14 (sCD14) and chitinase‐3‐like protein 1 (YKL‐40) using commercial ELISAs (R&amp;D Systems). Generalized estimating equations were used to evaluate the associations between serum biomarkers and longitudinal cognitive outcomes, as well as disease progression (CDR Sum of Boxes), adjusting for covariates of age, sex, ethnicity, education, body mass index, systolic blood pressure, diabetes, APOE ε4 status, and clinical diagnosis. Cox proportional hazard models were used to evaluate the associations between serum biomarkers and incident mild cognitive impairment (MCI) and dementia with adjustment for the covariates listed above.ResultAcross the average four‐year follow‐up period, 162 individuals developed MCI and 96 developed dementia (Table 1). As displayed in Table 2, serum GFAP levels predicted cognitive decline across most cognitive domains. Serum t‐tau levels were associated with declines in global cognition, learning, and memory. Serum GFAP (b=0.154, SE=0.028, p&lt;0.001), NFL (b=0.069, SE=0.026, p=0.007), and t‐tau (b=0.065, SE=0.023, p=0.004) predicted clinical progression. Higher GFAP levels at baseline were associated with increased risk of incident dementia (HR=1.485, p=0.009). None of the biomarkers predicted incident MCI.ConclusionSerum GFAP levels were associated with multi‐domain cognitive decline, clinical progression, and incident dementia risk. The results suggest that reactive astrogliosis may be an important mechanism underlying a progressive neurodegenerative disease course in our predominately Hispanic sample. With further validation, serum GFAP may hold utility for predicting disease progression and monitoring the efficacy of newly emerging treatments.

S100 Calcium-Binding Protein B and Glial Fibrillary Acidic Protein in Patients with Mild Traumatic Brain Injury.

Objective:To examine the GFAP and S100B ability in prevention unnecessary brain Computed tomography (CT) scan in mild traumatic brain injury (mTBI) and compare them with the single extremity fracture in orthopedic patients.Methods:In this prospective cohort study, two orthopedics patients’ groups and mTBI patients were studied to assess the biomarkers’ ability in prevention unnecessary brain CT scan at the emergency setting. There were 40 orthopedics’ patients with single extremity fracture and 41 mTBI patients. Brain CT scans were done for all mTBI patients. Results:Brain CT scans showed no intracranial traumatic lesions. The median levels for S100B in the mTBI group was 14.8 (4.4-335.9) ng/L, and in orthopedic patients’ group was 13.3 (5-353.10) ng/L. Statistically significant differences were observed between both groups in S100B levels (p=0.006). The median Glial Fibrillary Acidic Protein (GFAP) levels in the mTBI patients’ group were 600 (400-16300) and in the orthopedic patients’ groups was 60 ng/L (300-14900). Statistically significant differences were observed between groups in GFAP (p=0.041).Conclusion:Our results showed that S100B and GFAP serum levels were significantly higher in patients with mTBI than in patients with a single limb fracture.

Serum GFAP and NfL levels in benign relapsing-remitting multiple sclerosis

ObjectiveWe aimed to investigate serum glial fibrillary acidic protein (GFAP) and serum neurofilament light chain (NfL) levels as potential discriminative biomarkers between benign relapsing-remitting multiple sclerosis (BRRMS) and aggressive relapsing-remitting MS (ARRMS). MethodsSerum GFAP and NfL levels were analyzed in patients with BRRMS (n = 34), ARRMS (n = 29), and healthy controls (n = 14) by using Single Molecule Array (Simoa). Patients with ARRMS had been treated with highly effective disease-modifying treatments (DMT) (fingolimod or natalizumab). ResultsSerum GFAP levels in both BRRMS (median 210.19 pg/ml, IQR 163.69–287.19) and in ARRMS (median 188.60 pg/ml, IQR39.23–244.93) were significantly higher (p = 0.035 and p = 0.034, respectively) compared to healthy controls (median 117.93 pg/ml, IQR 60.28–183.83). Serum GFAP levels did not differ between BRRMS and ARRMS. There were no statistical differences in NfL levels between BRRMS, ARRMS and healthy controls. GFAP level was significantly higher (p = 0.04) in BRRMS without DMT (median 216.04 pg/ml, IQR 188.60–274.79) than in those BRRMS patients who had used DMT (median 196.26 pg/ml, IQR 133.33–325.54). ConclusionsWe found elevated levels of serum GFAP in both BRRMS and ARRMS compared to healthy controls, reflecting astrocytic activation. Serum NfL did not differ between BRRMS and ARRMS, probably due to the stable inflammatory phase of the disease and effective DMT use in ARRMS. Single serum NfL and GFAP measurements cannot separate a patient with BRRMS from effectively treated ARRMS after a long history of the disease, thus consecutive samples are needed in the follow-up.

Glial fibrillary acidic protein as blood biomarker for differential diagnosis and severity of major depressive disorder

Neuroinflammation has been connected to the pathophysiology of major depressive disorder (MDD) and neurochemical biomarkers of glial pathology could aid the diagnosis and might support patient stratification and monitoring in clinical trials. Our study aimed to determine the utility of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, for the differential diagnosis and monitoring of MDD. Employing Simoa technology we measured levels of GFAP in prospectively collected serum samples from 81 age-matched patients with MDD, schizophrenia (SZ), bipolar disorder (BP), and healthy controls (HC). Highest GFAP levels were determined for MDD. At a cut-off of 130 pg/ml, MDD could be discriminated with 87% sensitivity from SZ and BP (specificity 70%) and from HC (specificity 56%). GFAP levels increased with age (r = 0.5236, p = 0.0002) and with MDD severity quantified based on the Montgomery-Åsberg Depression Rating Scale (r = 0.4308, p = 0.0221). Neurofilament light chain serum levels were not different in the diagnostic groups and not associated with GFAP levels (r = 0.0911, p = 0.576) pointing to an independence of astrocyte activation on neurodegeneration. Our study provides first evidence that serum GFAP levels could improve the differential diagnosis of MDD and that depression severity could be objectively quantified using serum GFAP levels. Furthermore, serum GFAP might represent a marker to monitor astroglial pathology in the course of MDD.

The effect of aerobic exercise on Neurofilament light chain and glial Fibrillary acidic protein level in patients with relapsing remitting type multiple sclerosis

Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system in which disease activity can be monitored with some biomarkers. The aim of our study was to investigate serum Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NFL) in relapsing-remitting MS (RRMS) patients after the aerobic exercise.Methods A total of 38 participants with RRMS (Expanded Disability Status Scale: 1.0 – 4.5) were randomized to a study group (3 × /week for 8 weeks at 60 – 70 % of maximal aerobic capacity (VO2max) + home exercises) and a control group (were given home exercises programme 3 times a week for 8 week). Serum NFL and GFAP levels were analyzed using enzyme-linked immunosorbent analysis method before and at the end of 8 weeks.Results: NFL and GFAP levels were statistically lower in the study group at the end of the study than before the study. In the control group, no significant changes were observed in serum NFL and GFAP levels. ΔNFL levels were significantly higher in the study group than control group.Conclusion It was shown, for the first time that serum GFAP and NFL levels (%10 and % 32, respectively) in RRMS patients decreased after aerobic exercise. Our study is important in terms of investigating the effects of aerobic exercise in individuals with RRMS and elucidating the underlying measurable biomarkers. The significant reduction of NFL and GFAP, which have an important role in the pathology associated with nervous system damage in MS, with aerobic exercise may be promising in understanding the regulation of disease activity in MS patients.

Optical coherence tomography angiography indicates subclinical retinal disease in neuromyelitis optica spectrum disorders

Background: Neuromyelitis optica spectrum disorders (NMOSD) are neuroinflammatory diseases of the central nervous system. Patients suffer from recurring relapses and it is unclear whether relapse-independent disease activity occurs and whether this is of clinical relevance. Objective: To detect disease-specific alterations of the retinal vasculature that reflect disease activity during NMOSD. Methods: Cross-sectional analysis of 16 patients with NMOSD, 21 patients with relapsing-remitting multiple sclerosis, and 21 healthy controls using retinal optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), measurement of glial fibrillary acidic protein (GFAP) serum levels, and assessment of visual acuity. Results: Patients with NMOSD but not multiple sclerosis revealed lower foveal thickness (FT) (p = 0.02) measures and an increase of the foveal avascular zone (FAZ) (p = 0.02) compared to healthy controls independent to optic neuritis. Reduced FT (p = 0.01), enlarged FAZ areas (p = 0.0001), and vessel loss of the superficial vascular complex (p = 0.01) were linked to higher serum GFAP levels and superficial vessel loss was associated with worse visual performance in patients with NMOSD irrespective of optic neuritis. Conclusion: Subclinical parafoveal retinal vessel loss might occur during NMOSD and might be linked to astrocyte damage and poor visual performance. OCT-A may be a tool to study subclinical disease activity during NMOSD.