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Glial fibrillary acidic protein as a biomarker in neuromyelitis optica spectrum disorder: a current review

EXPERT REVIEW OF CLINICAL IMMUNOLOGY (2023)

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Article Clinical Neurology

A real-world study of interleukin-6 receptor blockade in patients with neuromyelitis optica spectrum disorder

Shu Yang et al.

Summary: This study evaluated the long-term effectiveness of tocilizumab in treating neuromyelitis optica spectrum disorder (NMOSD). The results showed that tocilizumab significantly reduced the relapse rate in patients with NMOSD, but high baseline plasma GFAP levels and prolonged infusion intervals may increase the risk of relapse.

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Review Clinical Neurology

Blood GFAP as an emerging biomarker in brain and spinal cord disorders

Ahmed Abdelhak et al.

Summary: Blood-derived biomarkers, such as glial fibrillary acidic protein (GFAP), hold promise in the diagnosis and prognosis of neurological diseases. However, there are limitations that hinder the widespread clinical use of GFAP as a biomarker.

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Article Clinical Neurology

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Pratishtha Chatterjee et al.

Summary: This study found that GFAP and p-tau have good diagnostic and longitudinal monitoring potential in preclinical Alzheimer's disease. Combining GFAP with other proteins can improve diagnostic accuracy.

ALZHEIMERS & DEMENTIA (2022)

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Article Medical Laboratory Technology

Pre-analytical stability of serum biomarkers for neurological disease: neurofilament-light, glial fibrillary acidic protein and contactin-1

Zoe Y. G. J. van Lierop et al.

Summary: The study found that most pre-analytical handling variations had little effect on NfL and CNTN1 levels, while GFAP showed good stability under all pre-analytical variables. For sample handling, it is recommended to store serum NfL at room temperature for up to 6 hours or at room temperature for up to 24 hours, and to perform a maximum of two freeze-thaw cycles for serum CNTN1.

CLINICAL CHEMISTRY AND LABORATORY MEDICINE (2022)

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Review Immunology

Serum glial fibrillary acidic protein is a body fluid biomarker: A valuable prognostic for neurological disease - A systematic review

Luana Heimfarth et al.

Summary: Astrocytes, as the most abundant cell type in the human central nervous system, play a crucial role in the regulation of neuronal physiology. This systematic review focuses on the potential use of glial fibrillary acidic protein (GFAP) as a blood biomarker for the detection of neurological disorders. The review summarizes studies published between January 2012 and September 2021 and highlights the association between elevated GFAP levels and various neurological diseases, suggesting its potential as a valuable diagnostic biomarker.

INTERNATIONAL IMMUNOPHARMACOLOGY (2022)

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Article Clinical Neurology

Silent progression of brain atrophy in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

Hiroki Masuda et al.

Summary: The research found that patients with NMOSD were older and had a higher disability status score at baseline MRI compared to those with MS. There were no significant differences in disease duration, annual relapse rate, and intervals from the last attack and from disease-modifying drugs initiation between the two groups.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2022)

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Article Immunology

CSF GFAP levels in double seronegative neuromyelitis optica spectrum disorder: no evidence of astrocyte damage

Jae-Won Hyun et al.

Summary: This study investigated whether double seronegative NMOSD (DN-NMOSD) and NMOSD with AQP4 antibody (AQP4-NMOSD) share the same underlying pathophysiology. The results suggest that DN-NMOSD has a different underlying pathogenesis compared to AQP4-NMOSD.

JOURNAL OF NEUROINFLAMMATION (2022)

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Article Clinical Neurology

Longitudinal follow-up of serum biomarkers in patients with neuromyelitis optica spectrum disorder

Hyunjin Kim et al.

Summary: This study evaluated the longitudinal clinical value of serum biomarkers in NMOSD patients, finding that serum GFAP may be the most appropriate for monitoring the disease activity. Further confirmation studies are warranted to validate these findings.

MULTIPLE SCLEROSIS JOURNAL (2022)

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Article Clinical Neurology

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

Lilian Aly et al.

Summary: Patients with NMOSD may experience subclinical retinal vessel loss, which could be associated with elevated levels of GFAP and lead to poorer visual performance. OCT-A may serve as a tool to study subclinical disease activity in NMOSD.

MULTIPLE SCLEROSIS JOURNAL (2022)

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Article Clinical Neurology

Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study

Pascal Benkert et al.

Summary: sNfL is a biomarker of neuronal damage used in monitoring disease activity in multiple sclerosis patients. This study established a reference database to correct for age and BMI, showing sNfL's potential in identifying individuals at risk for future disease activity. The results suggest that sNfL Z scores could predict acute and chronic disease activity in multiple sclerosis patients, with higher Z scores indicating increased risk.

LANCET NEUROLOGY (2022)

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

Eleni Rebelos et al.

Summary: Circulating levels of NfL and GFAP can reflect neuronal damage in obese patients. NfL may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

SCIENTIFIC REPORTS (2022)

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Article Clinical Neurology

Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder

Hisashi Murata et al.

Summary: This study highlights the role of cfDNA predominantly released by neutrophils in the induction of IFN-1 signature in NMOSD and identifies a novel pharmacologic target in NMOSD.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2022)

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Plasma Biomarkers of Neuropathogenesis in Hospitalized Patients With COVID-19 and Those With Postacute Sequelae of SARS-CoV-2 Infection

Barbara A. Hanson et al.

Summary: This study aimed to investigate the mechanisms of neurologic symptoms in COVID-19 patients and their relationship with related factors. The results showed biochemical evidence of CNS injury in both hospitalized and nonhospitalized patients, and anxiety was associated with the extent of neurologic damage.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2022)

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Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy

Itay Lotan et al.

Summary: The anti-IL-6 agents tocilizumab and satralizumab show promising results in active NMOSD, reducing relapse risk and pain severity, although their effects on fatigue differ. Adverse events are relatively mild. Further randomized, larger-scale trials are needed to determine their role in NMOSD treatment.

CURRENT NEUROPHARMACOLOGY (2021)

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Review Clinical Neurology

Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

Trygve Holmoy et al.

Summary: For NMOSD patients, monoclonal antibodies that deplete B cells or interfere with interleukin 6 signaling have superior efficacy compared to placebo; Rituximab, tocilizumab, and to some extent eculizumab have well-known safety profiles; Rituximab and azathioprine may be safe during pregnancy.

JOURNAL OF NEUROLOGY (2021)

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Review Immunology

Evidence for and against subclinical disease activity and progressive disease in MOG antibody disease and neuromyelitis optica spectrum disorder

Negar Molazadeh et al.

Summary: MOGAD and AQP4-IgG+ NMOSD are generally relapsing disorders with potential for prolonged periods of remission, unlike multiple sclerosis. Recent studies have explored evidence for progressive disease courses in these conditions.

JOURNAL OF NEUROIMMUNOLOGY (2021)

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Article Clinical Neurology

Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders

Yoshiki Takai et al.

Summary: The study classified astrocytopathy in AQP4-IgG+ NMOSD into four stages, each with unique pathological characteristics and clinical features. This staging system helps in understanding the unique temporal pathology of this disease.

BRAIN (2021)

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Reactive astrocyte nomenclature, definitions, and future directions

Carole Escartin et al.

Summary: The article highlights the challenges and uncertainties surrounding reactive astrocytes, advocating for comprehensive research that includes assessment of multiple molecular and functional parameters, preferably in vivo, along with multivariate statistics and determination of impact on pathological hallmarks in relevant models.

NATURE NEUROSCIENCE (2021)

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Review Clinical Neurology

A candidate biomarker of glial fibrillary acidic protein in CSF and blood in differentiating multiple sclerosis and its subtypes: A systematic review and meta-analysis

MengJiao Sun et al.

Summary: The study found that levels of CSF-GFAP are associated with MS and its different subtypes, reflecting varying degrees of astrocyte damage in different MS subtypes. Progressive MS is more closely linked to increased cerebrospinal fluid GFAP levels than relapsing-remitting MS, suggesting GFAP may be a useful marker of disease progression. Additionally, blood GFAP levels in MS patients are higher than those in the control group, warranting further verification with a larger sample size in the future.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2021)

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Article Clinical Neurology

Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

Oliver Schmetzer et al.

Summary: This study examined the role of anti-AQP4-IgG in patients with Neuromyelitis optica spectrum disorder (NMOSD). The results suggest that anti-AQP4-IgG may not play a predominant role in driving NMOSD, but rather may be associated with the disease and could be a relevant factor in only a subgroup of patients.

FRONTIERS IN NEUROLOGY (2021)

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Article Clinical Neurology

Discontinuation of Immunosuppressive Therapy in Patients With Neuromyelitis Optica Spectrum Disorder With Aquaporin-4 Antibodies

Su-Hyun Kim et al.

Summary: Discontinuation of IST in NMOSD patients may lead to an increased risk of relapse, even after 5 years of remission. Caution is advised when considering IST discontinuation, especially in patients who have experienced severe attacks prior to IST.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker

Orhan Aktas et al.

Summary: High serum GFAP concentration may be associated with NMOSD activity and attack risk, and may reflect treatment effects.

ANNALS OF NEUROLOGY (2021)

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Article Clinical Neurology

Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum

Andrea L. Benedet et al.

Summary: The study suggests that plasma GFAP is a sensitive biomarker for detecting reactive astrogliosis and Aβ pathology in early stages of AD, outperforming CSF GFAP. Plasma GFAP levels accurately discriminate between Aβ-positive and Aβ-negative individuals, with higher accuracy than CSF GFAP.

JAMA NEUROLOGY (2021)

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Article Pharmacology & Pharmacy

Sex Differences in Behavioral Symptoms and the Levels of Circulating GFAP, Tau, and NfL in Patients With Traumatic Brain Injury

Dilorom Sass et al.

Summary: This study found sex differences in TBI patients, with females showing higher levels of biomarkers and behavioral symptoms compared to males. The relationship between biomarkers and behavioral outcomes was more evident in females than males, suggesting a need for further research on individualized treatment guidelines.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Clinical Neurology

New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD

Yukio Takeshita et al.

Summary: This study evaluated the pathophysiology of NMOSD and the therapeutic mechanism of IL-6 blockade with satralizumab. The results showed that satralizumab can suppress the transmigration of T cells and barrier dysfunction induced by NMO-IgG, providing potential prevention of NMOSD onset.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Article Immunology

Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

Patrick Schindler et al.

Summary: This study suggests a potential role for sGFAP as a biomarker for disease severity and future disease activity in patients with AQP4-IgG(+) NMOSD during phases of clinical remission, while sNfL does not show significant associations in this aspect.

JOURNAL OF NEUROINFLAMMATION (2021)

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Article Immunology

Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies

Xuechun Chang et al.

Summary: sNfL and sGFAP levels were found to be significantly elevated in NMOSD patients compared to healthy controls, while the sGFAP/sNfL ratio could distinguish between different disease groups effectively.

FRONTIERS IN IMMUNOLOGY (2021)

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Editorial Material Clinical Neurology

The Calm Between Storms Serum Biomarkers in Assessing Interattack Astrocytopathy in Neuromyelitis Optica Spectrum Disorder

Carolyn Goldschmidt et al.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Investigating the Presence of Interattack Astrocyte Damage in Neuromyelitis Optica Spectrum Disorder Longitudinal Analysis of Serum Glial Fibrillary Acidic Protein

Jae-Won Hyun et al.

Summary: Subclinical astrocyte damage rarely occurs during interattack periods in individuals with NMOSD, but a certain degree of astrocyte damage does occur at the time of clinical attacks. Changes in sGFAP levels are more pronounced compared to sNfL levels.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease

Joana B. Pereira et al.

Summary: The study suggests that plasma GFAP concentration is associated with brain amyloid-beta pathology but not tau aggregation in Alzheimer's disease. This indicates that plasma GFAP may be incorporated into current hypothetical models of Alzheimer's disease pathogenesis and used as a non-invasive tool to detect early astrocytosis.

BRAIN (2021)

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Article Biochemistry & Molecular Biology

Serum neurofilament light chain and glial fibrillary acidic protein in AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and multiple sclerosis: A cohort study

Chunxin Liu et al.

Summary: The levels of sNfL and sGFAP were significantly elevated in patients with NMOSD and MS, aiding in distinguishing disease types and stages. sGFAP levels were associated with disease severity in NMOSD patients.

JOURNAL OF NEUROCHEMISTRY (2021)

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Review Neurosciences

Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair

Christopher G. Hart et al.

Summary: Astrocytes play essential roles in the development, maintenance, injury, and repair of the CNS. They have responsibilities in regulating blood flow, glucose metabolism, synapse formation, and axon myelination. In CNS pathologies, reactive astrocytes can exhibit both beneficial and harmful outcomes.

JOURNAL OF NEUROSCIENCE RESEARCH (2021)

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Article Clinical Neurology

Myelin-oligodendrocyte glycoprotein antibody-associated disease

Romain Marignier et al.

Summary: MOGAD is a recently identified autoimmune disorder characterized by CNS demyelination, distinct from multiple sclerosis and NMOSD. Diagnosis involves testing for anti-MOG antibodies and treatment is based on standard protocols for related conditions, with further evidence needed for optimal management strategies.

LANCET NEUROLOGY (2021)

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Article Clinical Neurology

Systematic Assessment of 10 Biomarker Candidates Focusing on α-Synuclein-Related Disorders

Isabel Schulz et al.

Summary: Objective diagnostic biomarkers are needed to support a clinical diagnosis of neurodegenerative disorders, with various markers being analyzed in serum and/or cerebrospinal fluid for alpha-synuclein-related disorders. Levels of most markers tested significantly differed between disease groups and healthy controls, with CSF NfL levels best discriminating between Parkinson's disease and multiple system atrophy.

MOVEMENT DISORDERS (2021)

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Article Clinical Neurology

Elevated chemokines and cytokines for eosinophils in neuromyelitis optica spectrum disorders

Li Du et al.

Summary: The study found that elevated serum MCP-1, -4, and CSF eotaxin-2, -3 may play a key role in eosinophil recruitment in the acute phase of NMOSD. Additionally, TNF-alpha and GM-CSF levels were higher in patients with NMOSD compared to those with other noninflammatory neurological diseases. Serum MCP-1 and -4 were significantly increased by IL-5 and GM-CSF stimulation, suggesting a potential mechanism for eosinophil recruitment in NMOSD.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2021)

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Article Clinical Neurology

A Kinetic Model for Blood Biomarker Levels After Mild Traumatic Brain Injury

Sima Azizi et al.

Summary: Traumatic brain injury (TBI) poses a significant burden on the economy and society, especially in the diagnosis and prognosis of mild TBI. Biomarkers play a crucial role in analyzing the brain condition after TBI.

FRONTIERS IN NEUROLOGY (2021)

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Article Clinical Neurology

Retinal Optical Coherence Tomography in Neuromyelitis Optica

Frederike Cosima Oertel et al.

Summary: This study highlights the importance of attack prevention to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies to ameliorate attack-related damage, especially during the first attack, are a clinical need. Mild neuroaxonal changes in ON-unaffected eyes may be solely due to contralateral ON attacks and do not indicate clinically relevant progression, but require further investigation.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder

Jie Li et al.

Summary: High-throughput sequencing and quantitative immunoproteomics were used to identify distinct AQP4-IgG lineages in NMOSD patients. The composition and polarization of these antibody repertoires may influence the pathogenesis and clinical presentation of NMOSD, with further potential applications in monitoring disease activity and understanding autoimmune diseases.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis

Alvaro J. Cruz-Gomez et al.

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Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis

Ting-Yi Lin et al.

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Longitudinal treatment responsiveness on plasma neurofilament light chain and glial fibrillary acidic protein levels in neuromyelitis optica spectrum disorder

Tian-Xiang Zhang et al.

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International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

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Glial but not axonal protein biomarkers as a new supportive diagnostic criteria for Devic neuromyelitis optica? Preliminary results on 188 patients with different neurological diseases

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Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures

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Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen

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AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance

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Neuromyelitis Optica: Pathogenicity of Patient Immunoglobulin In Vivo

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Intrathecal Pathogenic Anti-Aquaporin-4 Antibodies in Early Neuromyelitis Optica

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ANNALS OF NEUROLOGY (2009)

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Molecular dissection of reactive astrogliosis and glial scar formation

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Glial and neuronal damage markers in patients with anorexia nervosa

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Revised diagnostic criteria for neuromyelitis optica

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IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

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