When he ended his life last year by shooting himself in the chest, Junior Seau had a degenerative brain disease often linked with repeated blows to the head.
Researchers from the National Institutes of Health said the former NFL star's abnormalities are consistent with chronic traumatic encephalopathy, or CTE.
The hard-hitting linebacker played for 20 seasons with San Diego, Miami and New England before retiring in 2009. He died at 43 of a self-inflicted gunshot wound in May, and his family requested the analysis of his brain.
"We saw changes in his behavior and things that didn't add up with him," his ex-wife, Gina, said. "But [CTE] was not something we considered or even were aware of. But pretty immediately [after the suicide] doctors were trying to get their hands on Junior's brain to examine it."
The NIH, based in Bethesda, Maryland, studied three unidentified brains, one of which was Seau's, and said the findings on Seau were similar to autopsies of people "with exposure to repetitive head injuries".
"It was important to us to get to the bottom of this, the truth," Gina Seau added, "and now that it has been conclusively determined from every expert that he had obviously had CTE, we just hope it is taken more seriously. You can't deny it exists, and it is hard to deny there is a link between head trauma and CTE. There's such strong evidence correlating head trauma and collisions and CTE."
In the final years of his life, Seau had wild behavioural swings, according to Gina and to 23-year-old son Tyler, along with signs of irrationality, forgetfulness, insomnia and depression.
"He emotionally detached himself and would kind of 'go away' for a little bit," Tyler Seau said. "And then the depression and things like that. It started to progressively get worse."
He hid it well in public, they said, but not when he was with family or close friends.
Seau joins a list of several dozen football players who were found to have CTE. Boston University's centre for study of the disease reported last month that 34 former professional players and nine who played only college football suffered from CTE.
The NFL faces lawsuits by thousands of former players who say the league withheld information on the harmful effects of concussions. According to a review of 175 lawsuits, 3,818 players have sued. At least 26 Hall of Fame members are among the players who have done so.
The National Football League said: "We appreciate the Seau family's cooperation with the National Institutes of Health. The finding underscores the recognised need for additional research to accelerate a fuller understanding of CTE.
"The NFL, both directly and in partnership with the NIH, Centres for Disease Control and other leading organisations, is committed to supporting a wide range of independent medical and scientific research that will both address CTE and promote the long-term health and safety of athletes at all levels."
Seau is not the first former NFL player who killed himself and later was found to have had CTE. Former Chicago Bears defensive back Dave Duerson and Ray Easterling, who played for the Falcons in the 1970s, are the others.