In athletes who suffered a concussion, a protein in their blood may be able to predict when they can return to action. A new study finds that those who took longer to return to play had higher levels of a protein known as tau in their blood in the 6 hours following the trauma than players who were cleared to return to the field sooner. Tau blood testing isn’t ready for prime time, but experts say that if it pans out it would become an invaluable tool for coaches and physicians alike.
Trainers, sports physicians, and neurologists deal with some 3.8 million sports-related concussions in the United States each year. But they still lack an objective medical test to establish whether someone has sustained the injury, and at what point they have recovered enough from one to resume playing. Instead, they are forced to rely on often-nebulous physical signs, and on players’ self-reporting of symptoms. And it’s known that players, keen to get back on the field, often minimize these.
“We don’t want a biomarker that just says somebody had a concussion,” says study leader Jessica Gill, a neuroscientist at the National Institute of Nursing Research in Bethesda, Maryland. “We want a biomarker that says who needs to be out of play to recover.”
Gill, with concussion physician Jeffrey Bazarian of the University of Rochester School of Medicine and Dentistry in New York, and colleagues took preseason blood samples from more than 600 male and female University of Rochester athletes who participate in contact sports: football, basketball, hockey, and lacrosse. In it, they measured levels of tau, a protein linked to traumatic brain injury and Alzheimer’s disease, which has been found to be elevated in the blood of Olympic boxers and concussed ice hockey players. Then, in the 46 collegiate players who sustained concussions during the season, the researchers measured tau in the blood again—as they did in 37 uninjured, control athletes—at multiple time points: within 6 hours of the injury, and 1, 3, and 7 days later. (The concussions were witnessed by on-field, certified athletic trainers. The players’ symptoms also met the definition of concussion in a widely used test that evaluates symptoms like memory and balance.) Twenty-one nonathlete controls also had additional blood drawn and measured for tau, before the season.
Tau is so scarce in blood that it is notoriously difficult to measure. “It’s like looking for a couple grains of sand in an Olympic size swimming pool,” Gill says. So the researchers turned to a machine made by Quanterix of Lexington, Massachusetts, that uses magnetic beads coated by an antibody that binds selectively and extremely tightly to the protein in the blood.
As a group, the roughly 61% of the concussed athletes who weren’t cleared to return to play for more than 10 days had significantly higher concentrations of tau in their blood at 6, 24, and 72 hours after their injuries than did the players that experts said could return to the field sooner, the team reports today in Neurology. The biggest difference between the two groups was in the bloods taken within 6 hours of the athletes’ injuries.
Counterintuitively, in the group of athletes who were cleared to return to play sooner, the average tau level in the blood drawn within 6 hours after injury was actually lower than it was in the baseline, preseason blood draw. Possibly, this is because tau levels are known to rise, independent of injury, with exertion; thus the fall in tau from the preseason level may have reflected the players’ immediate, enforced rest after their injuries.
The nonathlete controls had lower levels of tau in their blood than the athletes at baseline, supporting the idea that exercise may lead to naturally higher tau blood levels. Why that may be is unclear, although the blood-brain barrier is thought to become more permeable during exertion; whatever the reason, the finding in the nonathletes will have to be accounted for if a blood test for tau as a measure of concussion severity is to become a reality.
The tau measure was also far from infallible. Blood tau levels within 6 hours after injury predicted with only 81% accuracy whether a given player would return to play in 10 days or less. What’s more, tau in the blood is only a proxy for tau in the brain, notes Barry Kosofsky, who directs the pediatric concussion clinic at Weill Cornell Medicine in New York City.
“The bottom line is they are measuring something in the blood that they hope is reflective of injury to the brain, but the signal may be obscured because it’s an indirect measure,” he says. He nonetheless calls the work “critically important” and says that an objective biomarker would be a “godsend” in his daily practice.
One avenue that needs exploring soon, says Gill, is whether other protein markers in the blood rise after concussions. Discovering those, she says, might fill out the picture, bringing that 81% to 100%.