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Review
. 2022 Mar 17:13:865730.
doi: 10.3389/fneur.2022.865730. eCollection 2022.

Glial Fibrillary Acidic Protein in Blood as a Disease Biomarker of Neuromyelitis Optica Spectrum Disorders

Hyunjin Kim  1 , Eun-Jae Lee  1   2 , Young-Min Lim  1 , Kwang-Kuk Kim  1
Affiliations
Review

Glial Fibrillary Acidic Protein in Blood as a Disease Biomarker of Neuromyelitis Optica Spectrum Disorders

Hyunjin Kim et al. Front Neurol. .

Abstract

Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein found in astrocytes in the brain. Damaged astrocytes release GFAP into cerebrospinal fluid and blood. Thus, GFAP levels in these body fluids may reflect the disease state of neuromyelitis optica spectrum disorder (NMOSD), which includes astrocytopathy, characterized by pathogenic antibodies against aquaporin 4 located on astrocytes. Recently, single-molecule array technology that can detect these synaptic proteins in blood, even in the subfemtomolar range, has been developed. Emerging evidence suggests that GFAP protein is a strong biomarker candidate for NMOSD. This mini-review provides basic information about GFAP protein and innovative clinical data that show the potential clinical value of blood GFAP levels as a biomarker for NMOSD.

Keywords: GFAP; NMOSD; anti-aquaporin-4 antibodies; biomarker; blood; glial fibrillary acidic protein; neuromyelitis optica spectrum disorder.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Glial fibrillary acid protein (GFAP) isoforms and (B) release of GFAP after astrocyte injury in neuromyelitis optica spectrum disorder. (A) GFAP protein consists of three domains: N-terminal head, central rod, and C-terminal tail. The head domain is crucial for filament assembly, the rod domain has a role in filament formation by coiling between polypeptides, and the tail domain is important in stabilizing the intermediate filament. (B) Serum anti-aquaporin-4 antibodies (AQP4-Ab) penetrate the blood-brain barrier and bind to aquaporin-4 (AQP4) on astrocyte endfeet. Antibody- and complement-dependent cellular cytotoxicity results in inflammatory cell recruitment, astrocyte damage, demyelination, and neuronal loss. After astrocyte damage, GFAP, an astrocytic scaffold protein, is released into interstitial and cerebrospinal fluid and finally reaches the blood through an impaired blood-brain barrier and/or glymphatic efflux.
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