A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults (original) (raw)
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A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children
Journal of Neuroscience Methods, 1992
In the present study we describe a sensitive ELISA for determination of glial fibrillary acidic protein (GFAP). To validate the method combined determinations of GFAP and S-100 protein were performed in cerebrospinal fluid (CSF) of normal children and children with autism. The GFAP ELISA is of sandwich type and uses the biotin-avidin system. Sensitivity was 16 pg/ml. Between-day precision was 0.079 (coeff. of varience). S-100 protein concentrations were measured using a commercially available ELISA kit. Normal CSF from children and young adults were analysed. The CSF levels of GFAP in normal children were low (16-163 pg/ml). Both GFAP and S-100 protein concentrations correlated with age (P < 0.01 and P < 0.05, respectively), but the GFAP increment was more pronounced, probably reflecting the age-dependent expansion of the fibrillary astrocytes in the central nervous system (CNS). GFAP levels in children with infantile autism were higher than those in normal children of the same age range. S-100 protein concentrations were similar in both groups. High levels of GFAP in combination with normal S-100 protein concentrations in CSF indicates reactive astrogliosis in the CNS. In conclusion, the sensitive ELISA described makes it possible to measure low levels of GFAP present in the CSF of children. Combined assays of GFAP and S-100 protein can be used to discriminate between acute and chronic brain disorders in children.
International Journal of Developmental Neuroscience, 2017
Brain specific-proteins are not found in other tissues and measurement non-invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain-specific protein values as brain damage markers in children with autism spectrum disorder (ASD). Method: 35 children with ASD and 31 healthy subjects were included in the study. Sociodemographic form and Childhood Autism Rating Scale (CARS) were applied to each subject. Serum neuron specific enolase (NSE), S100B, Myelin basic protein (MBP) and Glial fibrillary acidic protein (GFAP) values were measured with ELISA. Results: There was no significant difference between the two groups for NSE, MBP and S100 B values (p = 0.242; p = 0.768; p = 0.672, respectively). However, GFAP values in the patient group were statistically significantly higher (mean ± SD: 0.463 ± 0.392 ng/ml) than in the healthy control group (mean ± SD: 0.256 ± 0.111 ng/ml) (p < 0.001). In addition, there was a significant positive correlation between serum GFAP values and CARS score in all subjects and in the patient group (r = 0.599; p < 0.001 and r = 0.380; p = 0.024, respectively). Conclusions: While serum NSE, MBP, and S100 B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity.
Biological Psychiatry, 1993
The cerebrospinal fluid (CSF) of 47 children and adolescents with autism was analyzed for the contents of two astroglial proteins, the glial fibrillary acidic protein (GFA) and S 100. The results were contrasted with those obtained in similarly aged cases with other neuropsychiatric disorders (n = 25) and in normal children (n = 10). S-IO0 did not discriminate the groups from each other. However, GFA in autism and autisticlike conditions was at a level almost three times that in the normal group. The results could implicate gliosis and unspecific brain damage in autism. An alternative model would be increased synapse turnover regardless of underlying cause.
Blood Levels of Glial Fibrillary Acidic Protein (GFAP) in Patients with Neurological Diseases
PLoS ONE, 2013
Background and Purpose: The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. Comparably little, however, is known about GFAP release in other neurological disorders. In order to identify potential ''specificity gaps'' of a future GFAP test used to diagnose intracerebral hemorrhage, we measured GFAP in the blood of a large and rather unselected collective of patients with neurological diseases.
An ELISA for glial fibrillary acidic protein
Journal of Immunological Methods, 2004
Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein of the astrocyte, and body fluid levels of GFAP are an important tool for estimating astrogliosis and astrocytic activation in vivo. This paper presents a new sandwich ELISA allowing quantification of GFAP SMI26 from the cerebrospinal fluid (CSF). The sensitivity of the GFAP SMI26 ELISA is 5 pg/ml with a recovery of 94% and a mean within-and between-batch precision of 6% and 10%, respectively.
Plasma Levels of Glial Cell Marker S100B in Children With Autism
Physiological Research, 2019
Autism spectrum disorder (ASD) is a neurodevelopmental condition with increasing incidence. Recent evidences suggest glial cells involvement in autism pathophysiology. S100B is a calcium binding protein, mainly found in astrocytes and therefore used as a marker of their activity. In our study, children with autism had higher plasma concentrations of S100B compared to non-autistic controls. No association of S100B plasma levels with behavioral symptoms (ADI-R and ADOS-2 scales) was found. Plasma S100B concentration significantly correlated with urine serotonin, suggesting their interconnection. Correlation of plasma S100B levels with stool calprotectin concentrations was found, suggesting not only brain astrocytes, but also enteric glial cells may take part in autism pathogenesis. Based on our findings, S100B seems to have a potential to be used as a biomarker of human neurodevelopmental disorders, but more investigations are needed to clarify its exact role in pathomechanism of autism.
Blood GFAP as an emerging biomarker in brain and spinal cord disorders
Nature Reviews Neurology, 2022
In 2018, the FDA authorized the use of a blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in mild traumatic brain injury (mTBI), crowning a long success story of CNS-driven blood biomarker development 1-3. Initial efforts to identify fluid biomarkers for neurological diseases focused on the cerebrospinal fluid (CSF) as, compared with blood, CSF is closer to the brain extracellular space and contains higher concentrations of CNS-derived proteins 4. The establishment of fourth-generation immune assays in the last decade 3,5 brought the possibility of quickly obtaining rapid and robust protein biomarker measurements from blood samples, opening up new perspectives in the field of CNS-derived markers. For example, levels of classic CSF biomarkers of neuroaxonal damage, such as neurofilament light chain (NfL) 5 , phosphorylated tau 217 (ref. 6), and UCH-L1 (ref. 7) can now be readily quantified in blood, indicating that these markers hold potential for use in diagnosis and monitoring of disease activity, and as surrogate end points for treatment trials. The literature on the utility of blood GFAP as a biomarker is also growing, reinforcing the large body of published data on CSF GFAP 3,8-14. The evaluation of blood levels of GFAP has the potential to enable the in vivo longitudinal evaluation of different aspects of the astrocytic response in several neurological disorders. Here, we provide an up-to-date review of the analytical aspects, current evidence, perspectives, and limitations of blood GFAP as a biomarker, with the purpose of outlining how to refine its application in the diagnosis and monitoring of neurological diseases. GFAP biology and analysis Astrocytes represent around 30-40% of the cells in the CNS 15 , form an integral part of the blood-brain barrier (BBB) and establish numerous interactions with other cells in the nervous system, including neurons.
Glial Fibrillary Acidic Protein: GFAP-Thirty-One Years (1969–2000)
Neurochemical Research, 2000
It is now well established that the glial fibrillary acidic protein (GFAP) is the principal 8–9 nm intermediate filament in mature astrocytes of the central nervous system (CNS). Over a decade ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized
Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker
Trends in neurosciences, 2015
Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) III protein uniquely found in astrocytes in the central nervous system (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP mRNA expression is regulated by several nuclear-receptor hormones, growth factors, and lipopolysaccharides (LPSs). GFAP is also subject to numerous post-translational modifications (PTMs), while GFAP mutations result in protein deposits known as Rosenthal fibers in Alexander disease. GFAP gene activation and protein induction appear to play a critical role in astroglial cell activation (astrogliosis) following CNS injuries and neurodegeneration. Emerging evidence also suggests that, following traumatic brain and spinal cord injuries and stroke, GFAP and its breakdown products are rapidly released into biofluids, making them strong candidate biomarkers for such neurological disorders.