McKee, who is also director of neuropathology at Veterans Affairs Boston, began studying the brains of former NFL players 15 years ago. She couldn’t believe what she was seeing: large lesions in the crevices of the brain, studded with abnormal protein clusters. McKee is a big Packers fan and has seen many football games. But, she recalls, until then it had never occurred to me that they were damaging their brains, because you don’t see that on the field. They have the helmets. They look invincible.”
Researchers now know more about what happens to the brain under the helmet. The jostling of the brain pulls on nerve tissue, putting pressure on cells and blood vessels. Tau proteins, which stabilize the scaffolding that gives neurons their structure, fall off when a cell is under stress. These fallen proteins pile up in the cell, “a kind of toxic lump,” as McKee describes it. Ultimately, the buildup overwhelms and kills the cell, leaving neurofibrillary tangles that appear under a microscope as ominous dark streaks. This tangle, which also occurs in Alzheimer’s disease, makes it harder for neurons to communicate with each other, causing memory problems.
Meanwhile, damaged blood vessels compromise the sacred blood-brain barrier that normally protects sensitive nerve tissue from irritating molecules coursing through the rest of the body. The resulting irritation causes inflammation, which causes more tau clumping, starting a downward spiral of neurodegeneration.
To screen the brains of the donated young athletes for CTE, the researchers looked for tau, but also for signs of larger-scale problems such as inflammation, hardening or deterioration of blood vessels, and changes in the white matter, which contains the connections between neurons. They also interviewed the donors’ loved ones to learn about their behavior and cognitive symptoms during their lives. They had all experienced problems such as memory loss, depression and impulsive behavior.
Of the 152 brains examined, 63 were posthumously diagnosed with CTE. The vast majority were still in the early stages of neurodegeneration, but three of them – one from a former NFL player, one from a college football player and one from a professional rugby player – had reached the third of the four stages of CTE. Notably, another brain with CTE belonged to a 28-year-old collegiate women’s soccer player – the first case of its kind.
Thanks to the youth of these players, the research team was also able to rule out aging as a cause of the damage. Aging, as well as high blood pressure, heart disease and other neurodegenerative problems can all damage brain tissue. But in the sample used for the new study, all athletes between the ages of 13 and 29 died. “These are pristine, beautiful brains,” says McKee.
The fact that so many families of the donors had noted mood and memory changes – regardless of whether their child was ultimately diagnosed with CTE – could be an artifact of the study population. Families were simply more likely to donate to the brain bank if they had noticed unusual behavior in their child. But McKee says this also suggests that some of the symptoms these young athletes are experiencing are not always caused by CTE, but can still reflect the aftermath of head trauma. Chris Nowinski, co-author of the study and CEO of the nonprofit Concussion Legacy Foundation, remembers struggling with chronic symptoms after the concussion that ended his professional wrestling career in his 20s. In cases like his, concussion-related issues such as sleep problems, or the difficulties of coming to terms with life as an injured or retired athlete, are likely the root cause of the mental health problems – not necessarily tau pathology.