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VA research in action
Identification of the GFAP protein, used in brain-injury diagnosis
March 1, 2022
Photo: ©Getty Images/yacobchuk
Mild traumatic brain injury, also known as concussion, accounts for the majority of traumatic brain injury (TBI) cases. Mild TBI is the most difficult type of brain injury for clinicians to observe and diagnose.
In 1971, researchers at the VA Palo Alto Medical Center isolated a type of protein called GFAP (glial fibrillary acidic protein) that is now used to help determine whether a head injury may have resulted in brain damage that cannot be detected through computed tomography (CT) scans, the main diagnostic tool for brain injuries.
A test that detects GFAP in the bloodstream was approved by the Food and Drug Administration as a biomarker to aid in the evaluation of mild TBI in 2018. Biomarkers are measurable substances in the body that can help to determine whether an illness or other condition exists.
Protein detectable in blood when brain damage is present
GFAP, an acidic protein consisting of 432 amino acids, is found in astrocytes, which are supporting cells found only in the central nervous system, usually surrounding tiny blood vessels in the brain. In a brain injury, those small blood vessels can be damaged, leading to the leakage of the GFAP protein into the bloodstream. Since GFAP is usually found only in the brain, the protein’s presence in the body’s blood circulation indicates damage has taken place, even when CT scans do not detect any. If this protein does not show up in the blood, it’s likely that the head injury that was sustained did not result in any brain damage.
The VA research team first identified the GFAP protein and its presence in the central nervous systems of patients with multiple sclerosis. Other researchers, not affiliated with VA, later created a test that can detect GFAP in the bloodstream along with an enzyme called ubiquitin carboxyl-terminal esterase LI (UCHL1). That enzyme, like GFAP, not found in the bloodstream unless a patient has suffered a brain injury.
Brain Trauma Indicator approved by FDA
A blood test called a Brain Trauma Indicator is able to measure the levels of the two proteins within 12 hours of a head injury. Based on the results, clinicians are better able to determine the extent of the injury and to decide whether to order a CT scan. The results of the blood test are available in three to four hours, allowing for prompt treatment decisions that can minimize possible long-term effects of the injury.
In FDA testing, the Brain Trauma Indicator was able to predict brain injury 97.5% of the time, and the absence of brain injury 99.6% of the time. The Brain Trauma Indicator is now being marketed nationwide by Banyan Biomarkers, Inc.
Principal investigator: Dr. Lawrence F. Eng, VA Palo Alto Medical Center
Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI. Gill J, Latour L, Diaz-Arrastia R, Motamedi V, Turtzo C, Shahim P, Mondello S, DeVoto C, Veras E, Hanlon D, Song L, Jeromin A. Neurology, 2018 Oct 9;901(15):e1385-e1389.
An acidic protein isolated from fibrous astrocytes. Eng LL, Vanderhaeghen JJ, Bignami A, Gerstl B. Brain Res. 1971 May 7;28(2):351-4.
FDA authorizes marketing of first blood test to aid in the evaluation of concussion in adults. U.S. Food and Drug Administration news release, Feb. 13, 2018
Concussion biomarkers: where they stand now. AACC, Sept. 2020.