Glial fibrillary acidic protein (GFAP) TechNotes

Glial fibrillary acidic protein (GFAP) is a main structural protein of astrocytes (astroglia) of the central nervous system (brain and
spinal cord), and it is also found in nonmyelinating Schwann cells of the peripheral nervous system. It sustains the cell shape and participates in the regulation of processes related to cell proliferation, synaptic plasticity, as well as the function of the blood brain barrier.

Biochemistry of GFAP

GFAP belongs to a group of intermediate filament III proteins. To date, ten isoforms of GFAP have been described. However, it is only the predominant isoform (Isoform 1, or GFAP-α) that has been shown to have clinical significance (1). GFAP is a fibrillar protein of approximately 50 kDa. The formation of filaments includes the lateral dimerization of GFAP and head-to-tail polymerization of the dimers that are formed. The protein is highly conserved in different species and it is very similar to some other proteins that also participate in the formation of intermediate filaments, i.e. vimentin, desmin, peripherin and alpha-internexin.

GFAP as a marker in diagnostics

GFAP is a marker of glial cell injury. In circumstances where the glial cells are damaged, GFAP is released from cells and then appears in the blood. GFAP can be detected in blood samples shortly after the damage (2,3).

Differentiation between a hemorrhagic and an ischemic stroke. An increasing number of studies have indicated that GFAP might be a useful biomarker for the differentiation between a hemorrhagic and an ischemic stroke. Both can have severe consequences, but since these two forms of strokes have different mechanisms, they require opposite strategies of treatment. Therefore, it is important to find tools that help in terms of differentiating between the two strokes as early as possible. Studies have shown that GFAP increases in the case of a hemorrhagic stroke within two hours after stroke onset, with peaking taking place between 6 and 12 hours after stroke onset. Instead, in the case of an ischemic stroke, the GFAP levels in blood increase at a later time point (2,4).

Marker of traumatic brain injury (TBI). Emerging evidence has shown that GFAP could be used as a TBI biomarker. It was shown that in the case of mild and moderate TBI, GFAP levels demonstrate a marked increase eight hours after the trauma (3). In addition, the concentration of GFAP has also been suggested to predict the outcome of the injury (5). Furthermore, one test that measures GFAP (and UCH-L1) has been approved by the Food and Drug Administration for evaluating mild TBI (6).

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