The man who shot four people dead with an assault-style rifle inside a Midtown Manhattan skyscraper was carrying a "suicide note" blaming the National Football League for a degenerative brain disease he claimed to have, New York City's police commissioner said on Tuesday.

Police have identified the gunman as Shane Tamura, 27, a Las Vegas casino security officer and former high school football player with a documented history of mental illness.

Tamura killed two security guards, one of them a city policeman on security detail, as well as a real estate executive and a business management associate, before taking his own life on the 33rd floor of the Park Avenue skyscraper.

An employee of the NFL, which has its headquarters in the building alongside offices of major financial firms, was gravely wounded in the attack, which was the deadliest mass shooting in New York City in a quarter century.

The NFL worker was among several people shot in the lobby before Tamura, targeting the football league, used the wrong elevator bank and ended up in the 33rd-floor office suite of Rudin Management, a real estate company that owns the building, city officials said.

"A suicide note found in his possession at the scene spoke to a possible motive in the shooting and may explain why he targeted NFL headquarters," Police Commissioner Jessica Tisch said in a video message posted on YouTube on Tuesday.

In the note, Tamura "claimed to be suffering from CTE, possibly from playing high school football, and he also blamed the NFL," Tisch said. CTE, or chronic traumatic encephalopathy, is a degenerative brain disease.

The note, Tisch said, mentions a 2013 "Frontline" documentary featuring former NFL players who suffered from CTE, which has no known treatment and can be caused by repeated shaking of the brain associated with playing contact sports.

Linked to aggression and dementia, the condition can only be diagnosed conclusively after death.

"'Study my brain. I'm sorry,'" Tisch quoted Tamura as having written in the note.

The commissioner noted that Tamura had fatally shot himself in the chest.

The NFL has paid more than US$1 billion to settle concussion-related lawsuits with thousands of retired players after the deaths of several high-profile players.

It has made changes to the sport to mitigate the risk of concussions.

Tamura was never an NFL player, but he did play football during high school in California, according to school sports databases.

A former coach of Tamura, Walter Roby, told Fox News that Tamura was a "quiet, hard worker" and one of his "top offensive players" on the Granada Hills Charter School team. (Reuters)