Searching for Answers—One Brain at a Time
Searching for Answers—One Brain at a Time
Families who donate their loved one’s brain to BU’s CTE Center are helping researchers such as Ann McKee push the boundary of what we know about neurodegenerative diseases
Nick Cammarata had a booming laugh and an uncanny ability to spin out a story that kept people hooked, even as it went on…and on. But for Hayley Cammarata, it’s impossible to remember her older brother without thinking about hockey.
Nick excelled in youth programs in their hometown of Canton, Mass., tearing up the ice through middle and high school. He played Division I hockey at Merrimack College from 1999–2003, where he skated in 127 games, then played professionally for four years in the minor leagues—including a stint in Italy. Even after retirement, his life revolved around hockey: He coached junior teams in Utah, Texas, South Dakota, and New Hampshire.
“He loved hockey. He was this insanely talented athlete and hockey was the sport he fell in love with. He started playing when he was three years old, and he was amazing from that moment until he died,” says Cammarata. Nick died unexpectedly in June at age 44.
For all Nick’s beautiful qualities, there was another side to him—one that was more complex, more challenging, and seemingly only getting more so as time went on.
Hockey is a full contact sport, and after years of enduring hard hits, Nick worried that something was wrong—something in his brain. “He wanted to be involved in a CTE study if something should ever happen to him—and then, of course, something did happen,” Cammarata says, still sorting through the fog of grief.
After Nick died, the medical examiner connected Cammarata’s family with Sophia Nosek, research program manager and brain donation coordinator at Boston University’s Chronic Traumatic Encephalopathy (CTE) Center. Since its founding more than 15 years ago, the center has risen to be the world’s foremost seat of research into CTE, a neurodegenerative disease that is caused by repeated head trauma and can only be diagnosed after death—for now, at least. BU researchers have contributed immensely to the understanding of CTE—which has been tied to an array of symptoms, including memory loss, aggression, and anxiety—and helped countless families make sense of sometimes drastic cognitive and personality changes in their loved ones.
Nosek talked the Cammaratas through the donation process, asking a few preliminary questions about Nick’s life, and sending over consent forms. The medical examiner’s office handled the donation, and Nosek ensured it arrived in the lab in Boston. She let the family know Nick’s donation was safe, in hand.
Whatever comes, Cammarata says it will be a way to understand her brother a bit better.
And, she says, “If we can help find information for families in the future, it would be an honor for his legacy and for us as a family, to help future kids and families learn about this.”
The Power of a Phone Call
For Nosek, the phone call from Cammarata’s family was the first in a chain of toppling dominoes, where the end result is not just a diagnosis for one person, but also a growing body of research on a host of little-understood neurodegenerative diseases.
Once her phone rings, Nosek (CAMED’25) has just 72 hours from the donor’s time of death to coordinate the extraction of their brain, ensure it’s stable for travel and for the ensuing research, and organize its journey to Boston. It’s tight.
“I do feel like it’s one of the most important things I’ve ever done, because I need to speak to the families at some of the worst moments of their lives and make sure they feel comforted, as well as secure and confident in letting me handle something that’s really important to them and something that was really important to their loved one,” Nosek says.
Once it gets to the lab, that brain will join more than 1,500 others that, together, are helping to advance critically important scientific inquiry.
Ann McKee, who directs the CTE Center and is a William Fairfield Warren Distinguished Professor at BU, describes her team as world experts in CTE. It’s not an exaggeration.
The CTE Center is how we know that NFL star Aaron Hernandez, who was convicted of murder in 2015, had one of the most advanced cases of the disease ever found in someone so young. It’s how we know that NHL Predators team captain Greg Johnson had CTE. Roughly 70 percent of the brains studied by researchers at the center show evidence of CTE: scientists at BU have discovered it in young athletes who were just 17 years old when they died, and in older retired athletes, who were well into their 80s. Researchers have found it in nearly 92 percent of the ex-NFL players they’ve studied.
But it’s not just plaguing football and ice hockey: Rugby and soccer players have had CTE, along with rodeo and BMX riders. Boxers and wrestlers have had it, as well as military veterans. It’s been found in people with poorly controlled epilepsy and those who were victims of domestic violence. CTE can develop in anyone who experiences repeated hits to the head.
Researchers at the CTE Center have published more than 100 studies on CTE and traumatic brain injury—work that would’ve been impossible without the many donated brains. They’ve found that playing tackle football increases the chances of a Parkinson’s disease or amyotrophic lateral sclerosis (ALS) diagnosis, and that cumulative hits to the head can lead to a number of long-term consequences, including loss of white matter in the brain. Researchers at the center have also been key in figuring out the pathology of CTE—what it looks like in the brain and how the disease evolves over time. And all of these studies, researchers hope, will bring them closer to the Holy Grail of CTE research: being able to diagnose it in life, not just after death.
“Getting His Bell Rung”
Virginia Grimsley was folding laundry one afternoon at her home in Houston, Tex., when her ears perked up. It was the mid-2000s, and HBO’s investigative sports program, Real Sports with Bryant Gumbel, was airing an episode about the little-known long-term effects of repeated concussions on professional football players.
Grimsley turned the volume up. Her husband, John, had been a linebacker with the Houston Oilers (now known as the Tennessee Titans) and played in the NFL from 1984 to 1993. Football was known for its physical injuries, of course—torn ligaments, broken bones, and the like—but this was the first time Grimsley had heard anything about possible cognitive issues. Home alone, she watched the entire program front to back. Things started clicking into place.
High school sweethearts, Virginia knew that John had played football since he was eight years old. He would talk about “getting his bell rung” during particularly hard tackles, joking that afterward, he’d “aim for the guy in the middle” of his blurred vision. Players would inhale smelling salts, then get back on the field. The show, as it were, went on.
At one point after his retirement, Virginia asked John how many concussions he’d had throughout his career. He said he remembered three distinctly, but guessed it was closer to one a year during his professional career. Nine years. Nine concussions.
Thanks to research by scientists at the CTE Center, we now know that it’s not the number of concussions, but the number of hits to the head that causes CTE. John’s nine years in the NFL was enough of a proxy to raise concern.
And, for Grimsley at the time, it was clear that John had been acting differently lately. The once even-keeled, gentle man was suddenly quick to anger. He’d raise his voice, get frustrated easily. Plus, he’d been forgetting things. He needed directions to a friend’s house not five minutes away—a route he’d driven countless times.
“You notice these things, but don’t always know what it means,” Grimsley says now.
One weekend when she and the couple’s boys were away, tragedy struck. John, a lifelong outdoorsman, was cleaning his handgun—a meditative activity he’d do when no one else was in the house, and one he’d done hundreds of times before.
“Now, knowing everything that was going on in his head, he obviously forgot that you always check the chamber, to make sure the gun’s unloaded before cleaning it,” Grimsley says. “So that’s what happened. That’s how he died. It was an accident.” He was 45.
In the haze of those fitful days after John’s death—a tangle of urgent decisions no one ever wants to make—one decision now stands out to Grimsley as divine intervention, “a God thing,” she says: donating John’s brain to BU’s emerging CTE Center.
Emotional, Sensitive Work
In 2008, Ann McKee was studying professional boxers as part of her research at BU’s medical school. A neurologist and neuropathologist, she was more specifically looking into the deterioration she was finding in their brains—these athletes who had suffered one punch after another to the head during their careers. Under the microscope, their brain tissue was filled with an abnormal protein, called tau, that grew like so many weeds in a garden, tangling and strangling the healthy brain cells. What she found was more commonly known as “punch-drunk syndrome” at the time.
Then, a new donation came to her lab. In this brain, from John Grimsley, McKee found the same pattern of pathology she’d been finding in the brains of boxers. It was a stunning discovery, among the earliest anyone had made that found evidence of CTE in a former football player. John Grimsley became the fifth former NFL player to be diagnosed with the disease. And McKee pinpointed that abnormal, misfolded tau—in a very specific pattern and distribution in the brain—as a key indicator of CTE.
A year later, researchers at BU announced that they had diagnosed two more former NFL players, including former Tampa Bay Buccaneers offensive lineman Tom McHale, who was 45 when he died.
“We were college sweethearts,” says Lisa McHale, Tom’s widow. When they overlapped at Cornell, she helped manage the football team on which he played. Tom moved to Tampa to join the pros for the 1987 season, and Lisa followed a few years after. They got married in 2000.
McHale says that though her husband did show some signs of depression as he got older, she never knew him to have had a concussion; a few hard knocks, sure, but that comes with the territory. So when a researcher at the CTE Center called to ask about Tom’s brain shortly after his unexpected death, she assumed they needed a control sample.
“We know now that you don’t necessarily need to suffer a concussion to develop CTE,” McHale says. “The bottom line is Tom started playing football at eight and played a total of 26 years. That’s a long, long, long exposure.”
McHale joined the center two years after her husband’s diagnosis, pledging to help other people in her shoes. She’s now the center’s director of legacy family relations.
“It’s an emotional and very sensitive kind of work,” she says. “My conversations, the bulk of them occur with families who have suffered a very, very recent loss, many of them very tragically. And so it’s a constant reminder of the implications of this disease and a constant reminder of my own loss.”
The Gold Standard for Diagnosis
In her role now, McHale explains to families, including Cammarata’s, exactly what will happen with their loved ones’ donations, and why.
Once they’ve safely arrived, a technician will bisect the donated brain along its midline, setting aside one hemisphere to preserve in a chemical bath called formalin, and storing that half in refrigerators set to 4 degrees Celsius. Later, pathologists will slice thin slivers from this preserved tissue and use antibody staining to draw out details at a cellular level, under powerful microscopes. The other hemisphere is labeled, packed into plastic, and frozen at negative 80 degrees Celsius for future study.
At the cramped, mazelike Veterans Affairs facilities that host the CTE Center’s UNITE Brain Bank—a collaboration between BU, the VA Boston Healthcare System, and the Concussion Legacy Foundation—room after room is filled with industrial freezers, all humming at subfreezing temperatures. Each one contains hundreds of brains. It’s a scientific space—every nook and cranny is filled with tools and equipment, and the distinct, vinegary smell of the preservative bath is inescapable—but it’s also strangely moving. All these brains are quietly waiting to reveal a hidden story of their onetime owners and join in the crusade to better understand these vexing diseases.
Still, McHale tells her families, the research by the pathology team represents just half of the overall process.
A clinical team is also involved. They interview families and study the donor’s extensive health history: medical records, history of exposure to head injuries, any sports the donor played, for how long, and at what level.
The two teams, pathological and clinical, then compare notes. And while the ultimate diagnosis rests with the pathology results (the “gold standard” for diagnosis, McKee says), the clinical analysis can sometimes help families understand their loved one better. Beyond even that, the donations also enable researchers at the CTE Center to push the boundaries of our understanding of other neurodegenerative diseases, including Alzheimer’s disease.
For the family of a donor, a call from the CTE Center with their findings can resurface the grief of loss. “If we find CTE, that can be shocking—even if they were expecting it,” McKee says. “It can be very validating, though, too. It can be helpful in trying to understand why they may have acted the way they did, or why they may have done something that the family couldn’t understand.”
A Legacy That Keeps on Giving
In her role now, McHale is in touch with people who are where she and Virginia Grimsley once were: reeling from a loss, searching for answers. In some ways, she sees this as the silver lining in her loss. “It has helped me a great deal. I could have never imagined losing Tom and couldn’t have imagined moving forward from that. And so, in a lot of ways, [this work] has been a gift. It’s a real blessing that came from a real tragedy.”
Like Cammarata, Christina Mackesey is also waiting to learn more about her brother. Gabe “played heavy contact sports for a good majority of his life,” she says. Growing up in Saskatchewan, Canada, meant ice hockey was a given, but Gabe had a “very successful football career too.” He played football for roughly 15 years, and made it to training camp for the professional Canadian league. But, having suffered so many hits, Mackesey says, Gabe was showing worrying symptoms during training, like dizziness, loss of concentration, and headaches, which stopped his football career in its tracks.
Mackesey says she and her brother sometimes talked about his worry that he had CTE. Gabe didn’t elaborate on why, but Mackesey’s family had noticed some changes more recently that were out of character: his impulse control seemed diminished, for example.
In June, just about two months shy of his 43rd birthday, Gabe went into cardiac arrest, and Mackesey called the CTE Center hotline late on a Friday night. Nosek called back immediately, Mackesey recalls.
Nosek, McHale, and others from the center have been in touch every step of the way, Mackesey says, explaining in detail how this process works and the research that they’ll be able to do thanks to Gabe’s donation—and others like him.
“It’s been really special to my family to know that, yes, we are making a difference. Going forward, this is a way for Gabe to be part of every new breakthrough in CTE research, because his brain will be continually studied over and over and over.”
For Grimsley, the diagnosis was something of a relief. Neither Cammarata nor Mackesey say they’d be overly surprised if their brothers’ diagnoses are positive, either. The changes that didn’t make sense, the behavior that didn’t quite add up—maybe it will, soon.
Sixteen years after her husband’s death, Grimsley still smarts at the loss. And football, for better or worse, is still in the DNA. John had season tickets to Houston Texans games—tickets that are still in the family, Grimsley says.
“When he passed away, I didn’t want anything to do with football. But, also, it was his love. So, I still have the damn tickets, because the kids still like to go. I’ll tell you one thing though, my two grandsons are never playing football.”
The majority of funding support for the CTE Center and the UNITE Brain Bank comes from awards by the National Institutes of Health, as well as from the Department of Veterans Affairs, various industry groups, foundations, and private donors. The UNITE Brain Bank is a collaboration between the CTE Center, VA Boston Healthcare System, and the Concussion Legacy Foundation.
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