GFAP is a type-III intermediate filament and human GFAP comprises 432 amino acids, which are encoded by a gene on chromosome 17q21.1-q25. GFAP is the signature intermediate filament of astrocytes 17. Astrocytes are central to the normal function of synapses and contribute to axonal metabolic maintenance through the regulation of ion homeostasis 16 (Fig. 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.Īstrocytes 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. 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. 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, 9, 10, 11, 12, 13, 14. 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. For example, levels of classic CSF biomarkers of neuroaxonal damage, such as neurofilament light chain (NfL) 5, phosphorylated tau 217 (ref. 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. 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. 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, 2, 3. In our opinion, the clinical use of blood GFAP measurements has the potential to contribute to accelerated diagnosis and improved prognostication, and represents an important step forward in the era of precision medicine. We propose a model for GFAP concentration dynamics in different conditions and discuss the limitations that hamper the widespread use of GFAP in the clinical setting. In this Review, we provide a systematic overview of the evidence regarding the utility of blood GFAP as a biomarker in neurological diseases. Most importantly, the successful completion of the ongoing validation of point-of-care platforms for blood GFAP might ameliorate the decision algorithms for acute neurological diseases, such as TBI and stroke, with important economic implications. A growing body of evidence suggests that blood GFAP levels can be used to detect even subtle injury to the CNS. Evidence also indicates that blood GFAP levels hold the potential to reflect, and might enable prediction of, worsening of disability in individuals with progressive multiple sclerosis. In TBI, blood GFAP levels are correlated with clinical severity and extent of intracranial pathology. The test measures levels of the astrocytic intermediate filament glial fibrillary acidic protein (GFAP) and neuroaxonal marker ubiquitin carboxy-terminal hydrolase L1. In 2018, the FDA authorized a blood test for clinical use in the evaluation of mild traumatic brain injury (TBI). The introduction of highly sensitive immunoassays led to a rapid increase in the number of potential blood-derived biomarkers for diagnosis and monitoring of neurological disorders. Blood-derived biomarkers for brain and spinal cord diseases are urgently needed.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |