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BOSTON (AP) 鈥� The degenerative brain disease that has besieged the National Football League for two decades with a billion-dollar lawsuit, congressional hearings, an A-list movie and an unrelenting cortege of ex-players鈥� obituaries has now intruded on America’s favorite sport in the most violent manner yet.

The Las Vegas casino worker who killed four people in a New York City skyscraper that is home to the NFL’s headquarters carried a note blaming the league for mental health problems he attributed to his time as a high school football player.

Shane Tamura, 27, said in a three-page note found in his wallet that he had chronic traumatic encephalopathy 鈥� diagnosable only after death 鈥� and implored those who found him: 鈥淪tudy my brain.鈥� Among his grievances against the NFL was a claim that the league put its profits ahead of player safety by concealing the harm CTE, and football, can cause.

Echoing an eerie trend in NFL player suicides, he shot himself in the chest, preserving his brain for an autopsy that could confirm whether his layman’s diagnosis was correct.

A degenerative brain disease that has been linked to concussions and other head trauma common in military combat and contact sports, CTE has been diagnosed in more than 100 former NFL players and arisen as an existential threat to the United States’ most powerful pro sports league.

Its dangers have led some states to consider banning youth football, prompted leagues at most levels to limit contact drills in practice, and spawned a series of concussion protocols and other rule changes designed to take the most violent edges off the hard-hitting sport.

Here is what we know and don鈥檛 know about the connection between CTE, the NFL and the shooter.

What is CTE?

Chronic traumatic encephalopathy can affect regions of the brain involved with regulating behavior and emotions. This can lead to memory loss, depression, violent mood swings and other cognitive and behavioral issues, though researchers note that these symptoms can also be linked to other illnesses.

Experts say symptoms can arise years or decades after the last brain trauma. Evidence of the disease has been found not just in those with long professional careers but in high school athletes as well.

Why is it associated with the NFL?

Researchers have established a connection between CTE and contact sports, military combat and other activities with repeated blows to the head. After more than a decade of denial, the NFL conceded the link between football and CTE in 2016 testimony before Congress, and has so far paid more than $1.4 billion to retired players to settle concussion-related claims.

The 2015 Will Smith film 鈥淐oncussion鈥� detailed the pioneering efforts of forensic pathologist Bennet Omalu, whose diagnosis of CTE in Pittsburgh Steelers Hall of Fame center Mike Webster was the first in a former NFL player. Hall of Famers Ken Stabler, Frank Gifford and Junior Seau have also been diagnosed with CTE, as has Aaron Hernandez; in a 2017 paper, evidence of the disease was found 110 of the 111 former NFL players’ brains studied.

Did the NFL headquarters shooter have CTE?

It鈥檚 not possible to say.

For now, CTE can only be diagnosed definitively by examining the brain posthumously through an autopsy. According to Boston University鈥檚 Chronic Traumatic Encephalopathy Center, progressive degeneration of brain tissue in people with CTE includes the buildup of an abnormal protein called tau in a pattern that distinguishes it from other diseases such as Alzheimer鈥檚.

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Associated Press writers Maryclaire Dale and Laura Ungar contributed to this story.