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She never expected to get inside the head of the NFL. She thought she would become an internist and turned to neurology and neuropathology not to get away from people but to get closer to what makes them uniquely themselves. "They entrust me with their privacy, really," she says. "What a person's tissues look like, what struggles they were going through during life, and then what disease they have at death is a very private matter. That's as naked as you could possibly be. It's revealing yourself and revealing your internal structure."

For 25 years she studied tau in perfect anonymity, trying to understand its pivotal role in aging and Alzheimer's disease.

"Why tau?" I asked.

"Because it's pretty," was the artist/pathologist's reply.

The tau protein, named for the 19th letter of the Greek alphabet, is a naturally occurring substance in brain cells. Its job is to hold together microtubules, which are rigid, hollow rods like beach reeds that serve as conduits between brain cells. Tau provides "the scaffolding to support its shape and also to help transport molecules, nutrients, back and forth," McKee says. "Without tau the cell would collapse and the transport functions would be critically impaired."

With repeated head trauma tau turns insurgent, a guerrilla force occupying and killing more and more of the brain. "It falls off the microtubules, and so they fall apart too," McKee says.

Each concussive blow to the head — a right cross, a body check into the boards, a helmet-to-helmet collision in the open field, a header inside the goalie's circle — becomes a potential IED, a bomb hidden on a neural pathway. Think of it this way, she says: "This transport function of the cell is just like a road. And the road just fell apart."

Dementia pugilistica — punch drunkenness — first appeared in the medical literature in 1928. In 2002, Bennet Omalu, then a neuropathologist at the University of Pittsburgh, diagnosed the first known case of CTE in former Pittsburgh Steeler Mike Webster. He joined forces with Chris Nowinski, who procured three more donations, including former Eagle Andre Waters. All showed evidence of CTE.

In 2003, McKee performed an autopsy on a 72-year-old veteran who had been diagnosed with Alzheimer's disease 15 years earlier. She found toxic tangles of tau common to Alzheimer's and CTE, but they appeared in a totally unfamiliar pattern. And there was no evidence of the beta-amyloid plaques also present in Alzheimer's patients.

After the autopsy, she learned he had been a world-champion boxer. "That was the aha moment," she says. "I kept asking my colleagues if they had another boxing brain. I couldn't get it out of my mind."

McKee's laboratory does the neuropathology work for the Framingham Heart Study, the landmark multi-generational investigation into causes of heart disease. "I went back and stained all the Framingham heart disease cases we had, looking for a pattern of change that looked anything like this. I have drawers and drawers and drawers of these slides, and nothing looked like it.

"Then [in 2005] we got another through the Alzheimer's Center. There wasn't any history of head trauma. I went through all the medical records and nothing, so I got the name of the family. And I called the daughter, and she said, 'Well, he did box professionally in his 20s.' So, that was like, 'Okaaay.'"

In 2008 Nowinski came calling. He had parted ways with Omalu. He was also suffering the consequences of his WWE career, when he was known as Chris Harvard. Four wrestling concussions and two others on the gridiron had left him with severe headaches and impaired short-term memory — although he hasn't forgotten the taste of blood in the back of his throat that accompanied hits he took as a defensive tackle for the Crimson. (Thanks to a recent pickup basketball game, the count is now seven.)

He consulted Cantu about his symptoms. The doctor-patient relationship evolved into a professional alliance. They created SLI and later partnered with Robert Stern, director of Boston University's Alzheimer's Disease Clinical & Research Program, to create the Center for the Study of Traumatic Encephalopathy with the goal of acquiring and examining brains of deceased athletes exhibiting symptoms of premature dementia. All they needed was someone to do the autopsies. "Have I got the neuropathologist for you!" said Stern.

McKee sounds a lot like a football coach when she talks about her team at the Brain Bank, except, she says, her people give 400 percent. Over the course of three or four painstaking months, McKee's staff will cut half the brain into slices the thickness of white bread. They will use a high-tech deli slicer called a Microtome to shave 50-micron slivers of tissue — 0.001968 inches — which will shrink to less than half that size and be stained, fixed to slides, and magnified, perhaps 100 times, under the microscope.

"Handwork," she calls it.

Unstained, tau is unidentifiable. Staining makes the texture and the damage palpable. Some pathologists use a blood-red color to dramatize areas of disease. McKee favors brown, the color of dried blood.

On the day I visited, she spoke about the woman who prepared her slides for the last decade and whose devotion to her craft, despite failing health, was that of a mother hoping to find a way to protect her son. "An artisan," McKee calls her. "Like a person who makes a mosaic out of a million little pieces. It can take three or four hours just to lay the tissue out on the slide" — not including cutting and staining — "because you get it when it's wet and you have to manually smooth down every single teeny-tiny wrinkle."

John Grimsley, a linebacker who suffered three concussions in college and eight in the NFL, was the first NFL player whose tissue they examined. What McKee saw was so unprecedented in her experience that she twice asked Dan Perl to come look at the slides. It was a case of: Do you see what I see? He did. "When you look at the tangles, you say, 'Wow,'" Perl says.

While McKee and her staff dissect and preserve tissue, Stern, who oversees the CSTE registry, interviews family members to develop a case history: number of years and position played and in what decade, number of concussions suffered and symptoms noted. The most frightening finding is that "the biggest problem isn't the concussions, actually," McKee says. "It's the sub-concussive hits that mount up every single time these guys line up."

It's been estimated that there are 1,000 to 1,500 of those kinds of hits per season per person in the NFL. "A big job liability," she says.

In November, Stern received a $1.5 million grant from the National Institutes of Health to study 100 former players between ages 40 and 69 with symptoms consistent with CTE who played positions at the greatest exposure for getting hit in the head — defensive linemen, linebackers, offensive linemen, and defensive backs. The goal is to establish risk factors for the disease and genetic predisposition. "If we can figure out the genetic risk, we could be much smarter about informing individuals who are considering playing these sports what their relative risks are," McKee says.

Despite new NFL rules limiting the number of padded practices, and protecting defenseless receivers, the cumulative effect of violent collision remains dire. McKee believes there is "a window of reversibility" of perhaps one year before the disease has had "a chance to gain speed [and] cause the cells to die."

Stern: "With each brain that comes in, especially the younger ones, and especially the ones without any known significant history of concussions, but a whole lot of sub-concussive blows, that's where she gets really scared. That's where we all get really scared."

Posters hanging in the conference room show the sickening march of the disease — an 18-year-old who looked like he had cigarette holes burned in his brain; Owen Thomas, a junior and co-captain of the University of Pennsylvania football team who never suffered a concussion; Dave Duerson, who played 11 years in the NFL.

McKee has developed a four-tier system for staging the disease that first invades the front cortex — the province of judgment, insight, inhibition, and concentration — and then begins to "work its way inward, penetrating the essence of a person."

Staging is determined by the amount and distribution of tau. In Grade 1, a few hot spots appear on the surface, clustered around small blood vessels. "You see those holes on the side walls, the holes and tangles in a circle around the hole?" she says, pointing to Owen Thomas's damaged brain tissue. "That's a 21-year-old brain!"

The blood vessels vex her and perplex her. "Why the blood vessels?" she says, tracing a painterly splatter on his brain with her forefinger. "What am I missing?"

She was talking to the disease, not to me.

In Grade 2, the spots multiply but most brain tissue is undisturbed. Thomas had Grade 2 of the disease when he committed suicide; the 18-year-old had Grade 1.

In Grade 3, the neurofibulary tangles she likens to skeins of unraveling yarn invade multiple lobes of the brain. Besieged, the medial temporal lobe atrophies. The hippocampus, essential for learning and memory, is attacked. The amygdala, which governs aggressiveness and rage, is assaulted. Symptoms multiply and intensify: headaches, depression, insomnia, anxiety; loss of impulse control, executive function, and emotional regulation; tremors, vertigo, slurred speech and a staggered gait; and finally dementia.

A slide of Dave Duerson's tissue demonstrates the awfulness of Grade 3 CTE. Under the microscope his brain tissue looks like the bark of a tree. "You see all those little spots of damage?" McKee says. "And he doesn't even have the worst case of this. This is really substantial disease, especially since he's only 50."⁴

Women lose lovers, friends, husbands, partners. Men lose their way, their memories, their lives. Ministers forget verses from the Bible. Hall of Famers fail to recognize themselves on trading cards. Outpatients get lost en route to the doctor. "A lot of ex-wives step in to help their ex-husbands," says Culverhouse, who created the Players' Outreach Program in Tampa Bay to provide health care and disability benefits for former players. She has an Ed.D. from Columbia University, a terminal illness, and a history of concussions from falling off too many horses. (She, too, has promised her brain to McKee.) Her clinic schedules appointments on Saturdays so players aren't recognized. "One of the ex-wives set the GPS so her former husband could get to our medical center," she says. Hours after his appointment, one of the nurses found him driving around the parking lot in circles. "No one had reset the GPS."

With each new report about reckless, homeless, abusive players, drug addiction and suicide, McKee wonders: How much is attributable to brain disease and how much to the corrosive effect of celebrity and entitlement on a particular personality structure?

"There are horrible life changes in terms of memory, emotion, and lack of impulse control, which heaps gobs of negativity on them, divorce, addiction, businesses that fail," Cantu says. "It's a vicious cycle, a perfect storm. The final event for those that die young is not the brain damage per se but what the brain damage has led them to do, which is what caused Dave Duerson to put a gun to his chest."

Duerson's last conscious act was to preserve his brain for science. That choice, Cantu says, also guaranteed a very painful death.

The most affecting of McKee's visual aids is a triptych she created documenting the progression of the disease. When she paints, she prefers oils, figurative painting. This digital portrait is deconstructed 21st-century abstract art.

The first panel, a slice of healthy brain tissue, reminds me of one in a series of Sam Francis paintings called "Blue Balls" but rendered in purples and whites. The second panel, a section of John Grimsley's brain, looks like a Jackson Pollock — Shimmering Substance, perhaps. The last panel from the boxer, who was her patient zero, calls to mind Willem de Kooning's Excavation.

The images have entered the public domain and the collective sporting unconscious thanks to permissions granted by family members. Still, Virginia Grimsley had the wind knocked out of her one day a year or so after her husband's death when she saw one of McKee's brain images flash across the TV screen: John's brain. She reminded herself — "It's good. It's all good. It has to come out."

Then she left a message for Nowinski. "You might want to warn the families."

Nowinski had hand-delivered John's slides to Houston in advance of the Family Conference, a conference call with family members during which she and Stern present their findings. Grimsley doesn't remember much from that time. Her synapses were snapped when her 45-year-old husband, a lifelong hunter, accidentally killed himself while cleaning a new gun. She now believes that he forgot that there were bullets in the chamber. She asked her boss, a pediatrician, to be on the call when she got the results from Stern and McKee. But it turned out Grimsley didn't need a translator because, she says, McKee is "so plain-English."

For McKee, the Family Conference is her first chance to fill the holes in the lives she sees under the microscope. For the wives, mothers, and daughters she calls "the crusaders," it is an opportunity to reclaim their loved ones from memories and reputations ravaged by disease.

"They're the only witnesses, which is also what intrigues Ann," Nowinski says. "The worst things are only seen by one person, and these stories never would see the light of day without them."

This is when she feels most like a clinician. "I'm being a doctor to people, but now the people are the families they've left behind."

She is asked "a million questions," Nowinski says, and stays on the line as long as there are answers she can give. "She allowed me to talk," Grimsley says simply. "I think she got a sense of who John was. This is not just brain tissue to her. This is someone's life, someone's memory, someone's husband, someone's son, someone's father."

After two and a half hours, Grimsley finally had a way to understand how a man who made his living as an outdoor guide ending up shooting himself to death. For the first time since his death in February 2008, she could exhale.

Tom McHale's slides arrived by mail at his widow's home along with a caution from McKee: "You might want to wait to open them until we are on the phone together."

Lisa McHale couldn't wait.

The impact was concussive. Her body shook. Her mind went blank.

McHale, who now works as a liaison between families and SLI, had been so sure they wouldn't find anything; so positive he had never suffered a concussion during nine years as an NFL offensive lineman. But doctors at the drug rehab center where he was treated for repeated relapse, depression, and irritability had no answers for them. "You seem to have embraced all that we have," a doctor told Lisa and Tom days before his death. "I've treated professional athletes before and I've had a similar problem, and I don't know what the problem is. Maybe it's the humility thing. Maybe you just can't reach that level of humility."

Lisa thought: You don't know my husband at all.

But she was no longer sure she ever knew him. Where was the sweet boy she met in college at Cornell? Who was this addict who used drugs with their three children in the house? Who succumbed to the overdose that killed him after Lisa told him he had to leave? Maybe I just remember Tom wrong, she thought. Maybe I glamorized him — because nobody's that good, and nobody changes that much.

After McKee presented her findings, McHale told her: "You gave me back my Prince Charming."

Sylvia Mackey heard from McKee and Stern two weeks before the Super Bowl in February, seven months after the death of her husband, John, the Hall of Fame tight end, no. 88 for the Baltimore Colts. She was the moving force in the creation of Plan 88, which pays $88,000 a year toward the care of players with dementia, and she is still fighting for the benefits she and other widows are due. She wasn't apprehensive about receiving McKee's report — she was relieved that the results confirmed what she already knew inside. Her 45-year-old son cried.

She says the diagnosis of CTE and frontal temporal dementia explained John's fixation with what she calls his "man bag," a black leather shoulder bag he took everywhere, including to Bobby Mitchell's charity golf tournament in Washington, D.C. "You couldn't touch it," she says. "At a photo session, a lady reached for it and he pushed her back and cursed at her. It was the last time he was invited."

The bag contained the Sharpies he used to sign his autograph: John Mackey, no. 88. The prosaic tools of the celebrity trade were a reminder of who he had been. "We had to send that bag to the assisted living facility," she says. "Finally he forgot about it."

By then he couldn't remember anything at all.

On June 18, Eleanor Perfetto called Nowinski to make arrangements for her husband's brain to be delivered into McKee's care. Ralph Wenzel, who was 69, had been institutionalized since early 2007. Perfetto had long considered herself a widow.

Ralph disappeared little by little after being diagnosed with dementia in 1999. "One morning he got up and went into the bathroom before I could get him dressed," she says. "He came back and said, 'I need to get dressed. There are people in the bathroom.'"

Perhaps he was confused by his own nakedness. The doctors weren't sure.

By Christmas of 2006, belligerence had supplanted hallucination and delusion. He went to live in a lockdown facility. A month later, Perfetto and Wenzel gave an interview to Bernard Goldberg of HBO's Real Sports, though she did all the talking. By then, Wenzel, a high school physical education teacher in his second career, could barely speak. "He hadn't spoken the whole day," Perfetto says. "They probably filmed him six or seven hours. They were hauling the equipment out of the facility. He walked up to Bernie like he wanted to say something. Bernie said, 'Yes, Ralph, what is it?'

"Ralph looked at him very seriously and he said, 'The kids. The kids.'"

Ann McKee doesn't sleep.

"How could she?" Mackey says.

Complete brain rest, the prescription for concussed athletes, is not an option for her. "I wake up in the middle of the night and I work," she says. "I get up and write part of a grant proposal. I dream about their slides. I dream about their lives. I can't put this to bed."

Painting is her refuge — the one place in her life that tau has not infiltrated. She works with a private instructor at an art studio and tries to get there twice a week. "The reason I love art is if you're really painting you are not thinking about this," she says, nodding at an example of brain portraiture. "You have to completely spiral your brain in a different direction. Once you get into that zone, you're resting your brain. I still struggle with this work being very analytical and art being very non-analytical. So to put the two together is a real brain cramp."

She says her house and garden are a wreck. She's embarrassed to have people over. Nowinski sees the toll elsewhere. "She covers it up incredibly well in public," he says. "But there's times she talks about how this research is slowly killing her."

In October 2011, McKee and Kevin Turner were honored at the fourth annual SLI Impact Awards dinner in Boston for their work on behalf of brain-trauma awareness. Turner, a college star for the Crimson Tide and fullback for the Patriots and Eagles, was embarrassed to share the award with her. "What did I do?" he says. "I just got diagnosed with ALS."

Turner, the subject of a new documentary, American Man, was diagnosed with amyotrophic lateral sclerosis — Lou Gehrig's disease — in May 2010. Two months later, McKee published a study linking traumatic brain injury with an ALS-type disease, which she has subsequently documented in 11 athletes, amateur and professional.

Turner was among 40 to 50 athletes at the banquet who had promised their brains to McKee. But unlike most of them, he is unlikely to survive her tenure at the Brain Bank. As he accepted a hug and a plaque, he knew that the woman with whom he shared the podium and an embrace will someday receive a Styrofoam box containing his brain and spinal cord. "I want her to use it all," he says.

The guests included family members of traumatic brain injury victims — Perfetto, McHale, and Mackey among them — and athletes of every age and pursuit. "Most were men, and they wanted to meet her because to them, she's a rock star," Nowinski says. "She's the person they're trusting their legacy to. They trust her to take care of their brain and how they're remembered. So I had everybody line up in a receiving line as she went up to the podium to accept the award. Everybody cried. Everybody got a hug."

I reached Kevin Turner in his pickup truck at a fast-food drive-in in Birmingham, Alabama. He was grabbing a sandwich en route to his younger son's basketball game. He pulled his boys out of football after listening to Cantu explain the vulnerability of the brain between ages 6 and 14, which made him less popular than he once was in Birmingham. He will allow his older son, Nolan, to return to the field this fall for freshman year in high school once he turns 15. "My youngest, he's 8," he says. "He doesn't know it yet, [but] he's going to take a break until high school."

By the time I caught up with Turner again six months later, Cole had turned 9 and was complaining bitterly about playing flag football instead of "real football." Things had gotten harder for his father too. He can no longer zip his pants or get himself a glass of water or reach into his pocket for his wallet. (He carries a bag now.) His sons know where he keeps the credit cards. They pump the gas and help change the gearshift when dad is driving, as he was when I reached him again.

He pulled over so we could talk, and a police officer stopped to make sure he was OK. Turner told him he was fine. "I can still breathe, so I can't complain," he says.

He still lives alone but is looking to hire someone to be his hands. He can't rely on his daughter and sons anymore. He doesn't go out to eat much. It's hard to get a fork in his mouth, to get to the bathroom in time, to change the channel on the remote, to answer the telephone. A lot of calls go unanswered.

In June, talking was a problem. It's better now. "One day it felt like there was something in my mouth. I was trying to spit it out," he says. "It felt like I had just come out of the dentist. I couldn't feel my lips."

Turner told me in February that he hoped to visit McKee's lab to see where the work is done. He wondered "what they'll be saying when they're digging into my head — 'here's one of his dumb jokes. We need to take that part out.'"

He also said he was worried that knowing him will make McKee's job more difficult. He wants to have a conversation with her, perhaps in September when he is scheduled to attend a conference in Boston on traumatic brain injury and ALS. "I think I know what I'm going to say," Turner told me. "I'd hope I'd say, 'I'm so happy it's in your hands. I want you to be smiling and thinking about how much fun I had my whole life.' I don't want her to have a bad day at the office."