Levels of certain proteins in the blood may act as concussion biomarkers

A concussion diagnosis depends upon a careful assessment of symptoms. Now a large study of sports-related concussions points to a potential medical assist when evaluating a college athlete for this injury.  

Certain proteins in the blood are elevated after a concussion, researchers report online January 24 in JAMA Network Open. That discovery may one day help with distinguishing athletes who have suffered this brain injury from those who haven’t.

Researchers took blood samples pre- and post-injury from 264 college athletes who had concussions while playing football, rugby and other contact sports from 2015 to mid-2018.  Blood levels for three proteins were higher than they were before the injury occurred, the researchers found.

Each of the three proteins can serve as a sign that damage has occurred to a different type of brain cell, says Michael McCrea, a neuropsychologist at the Medical College of Wisconsin in Milwaukee. Glial fibrillary acidic protein is released in response to injury to glial cells, which provide support to nerve cells in the brain. Ubiquitin C-terminal hydrolase-L1 signals that nerve cells have been injured, and tau is a sign of damage to axons, which transmit nerve impulses. These proteins have been evaluated in past research as potential markers of more severe traumatic brain injury.

McCrea’s team also measured these proteins in 138 athletes who played contact sports but were not concussed, and in 102 athletes who did not have the injury and played noncontact sports. The protein levels for these two groups remained steady throughout the study. If there had been large variability in the protein levels in non-concussed athletes, McCrea says, that would have undermined the association between the proteins and concussion.

Traumatic brain injuries — which can result from a blow to the head during falls, car accidents or while playing sports, for example — can range from severe to mild. Sports-related concussions are considered mild traumatic brain injuries, McCrea says. An estimated 10,560 sports-related concussions are reported by college athletes in the United States each year, according to a 2015 American Journal of Sports Medicine study.

A person suffering a concussion generally experiences one or more of the following symptoms: headache, nausea, dizziness, confusion and a brief loss of consciousness. But the physical symptoms may not always make the diagnosis clear; a headache after a tackle might not necessarily be a sign of concussion. So researchers have been looking for chemical signals, called biomarkers, that may help reveal when a concussion has happened.

It will take much more work before concussion biomarkers would be ready to use in the clinic or on the field, McCrea says, including determining which combination of proteins are most reliably linked to the injury and how to quickly test for them.  

“The goal of a biomarker is to provide a reproducible and accurate indicator of a medical state,” says Juliana VanderPluym, a neurologist at the Mayo Clinic in Phoenix, Ariz., who was not involved in the study. She notes that “it is important to consider [biomarkers] as an aid, and not necessarily as the final determinant” of a diagnosis. For example, if an athlete gets tackled in a game and reports symptoms that suggest a concussion, she says, but has normal levels of these proteins, should that athlete be allowed to return to the game? “These are questions that we will need to address before biomarkers become part of clinical practice.”

Around 80 percent of the study participants were male athletes. “It will be important in future studies to see whether the results are similar” for women, says VanderPluym. Female college athletes have a higher rate of concussions than males, according to a 2016 study in the Journal of Athletic Training. Women also can experience more severe symptoms after a blow to the head than their male counterparts and may experience worse damage to the brain (SN: 7/31/18).