By Cassandra Willyard

On February 17, retired American-football player Dave Duerson committed suicide. The 50-year-old former defensive back for the Chicago Bears left this haunting note for his family: "Please, see that my brain is given to the NFL's brain bank." Then he shot himself in the chest, leaving his brain intact.

The brain bank Duerson referred to, located at Bedford VA Medical Center in Massachusetts, is funded by the U.S. National Football League (NFL) and run by Ann McKee, co-director of the Center for the Study of Traumatic Encephalopathy at Boston University in Massachusetts. She and her colleagues have spent the past several years examining athletes' brains for signs of a neurodegenerative condition called chronic traumatic encephalopathy (CTE).

Whether Duerson had the disease is still unknown. But his note seems to imply that he feared the worst. Nature examines what researchers know about CTE, what they have yet to understand and what is being done to protect athletes.

What is chronic traumatic encephalopathy?

CTE is a neurodegenerative disease caused by repeated trauma to the head. "The head trauma usually occurs years, maybe even decades before the person become symptomatic," McKee says.

Symptoms of CTE tend to appear in midlife, after most athletes have retired. The signs may be subtle at first--apathy, depression, irritability. "A lot of times the spouse will notice that the husband--usually it is the husband--just isn't the person she married," McKee says. "They may have a short fuse. Small things make them go off." CTE can also cause cognitive problems and memory lapses. As the disease progresses, individuals with CTE may develop tremors, speech problems or dementia. Suicide and erratic behavior also seem to be associated with the condition.

Who is at risk?

Signs of CTE were first observed in boxers more than 80 years ago. Back then, trainers described affected fighters as being "punch drunk" or "slug nutty." The first evidence of CTE in an American-football player emerged in 2002, when neuropathologist Bennet Omalu, now co-director of the Brain Injury Research Institute at West Virginia University in Morgantown (which houses a separate brain bank), examined the brain of former NFL player Mike Webster.

"Anyone who is exposed to mild repetitive head trauma is vulnerable," McKee says. That includes American-football players as well as rugby, football (soccer) and hockey players, boxers, wrestlers, soldiers, victims of physical abuse and 'head bangers' at rock concerts. A 2009 review by McKee and her colleagues published in the Journal of Neuropathology and Experimental Neurology even includes a case of CTE in a person with dwarfism, who had been knocked out a dozen times while participating in "dwarf-throwing" contests.

Researchers are still trying to sort out how many hits it takes for an individual to develop the disease and how forceful those hits have to be. Worryingly, McKee's research suggests that even multiple mild blows that don't cause symptoms of concussion may be enough to trigger CTE. And some people may be more susceptible genetically than others.

How is the disease diagnosed?

The only way to definitively diagnose CTE is though a post-mortem examination of the brain. The disease leaves a distinct signature: microscopic clumps of tau proteins. Normally, tau proteins help to stabilize the hollow tubes called microtubules that help give cells their shape. But in patients with CTE, the tau proteins become tangled. This happens in the brains of people with Alzheimer's disease as well, but the two conditions are distinct. People with CTE don't have the extensive plaques characteristic of Alzheimer's disease. And their tau clumps tend to be patchier, McKee says.

McKee and her colleagues hope to be able to identify CTE in living athletes. One promising avenue of research involves searching for biomarkers such as tau proteins in the cerebrospinal fluid of patients. Brain-imaging techniques such as functional magnetic resonance imaging (MRI) or diffusion tensor MRI might also prove useful, she says.

How common is it?

No one knows. In a paper published this year, McKee and her colleagues note that 321 professional football players died between February 2008 and June 2010. The team examined the brains of 12 of those players. All 12 showed signs of CTE.

What is being done to reduce the risk of CTE?

The NFL acknowledges that a link exists between head injuries sustained on the field and the onset of neurodegenerative diseases later in life. In 2009, the league implemented a rule that players exhibiting any sign of concussion must be sidelined for the day. And on 23 February, the NFL announced that next season it will use a new evaluation tool to diagnose concussions that will include a symptom checklist, a limited neurologic exam and cognitive evaluation, and a balance assessment.

Still, eliminating head injuries from football or other contact sports could prove exceedingly difficult, says Gary Solomon, a neuropsychologist at Vanderbilt University in Nashville, Tenn. "I don't think we're ever going to have a concussion-proof helmet."