The man who killed four people in a rampage with a rifle through a Midtown Manhattan office building blamed the National Football League for his degenerative brain disease, New York Mayor Eric Adams said.

Police have identified the shooter as Shane Tamura, a 27-year-old Las Vegas resident with a history of mental health struggles.

Trump calls NY shooting that killed four a 'senseless act of violence'. – Reuters

The NFL has its headquarters in the skyscraper, but Tamura apparently entered the wrong elevator bank and ended up in the offices of Rudin Management, a real estate company, where he shot employees, the mayor said.

"He felt he had CTE, a known brain injury for those who participate in contact sports," Adams told CBS News. "He appeared to have blamed the NFL for his injury."

Chronic traumatic encephalopathy is a serious brain disease with no known treatment that can be caused by repeated bangs to the head from contact sports. It has been linked to aggression and dementia, and the NFL has paid an estimated $1 billion to settle concussion-related lawsuits with thousands of retired players after the deaths of several high-profile players.

Tamura played high school football in California nearly two decades ago, but he never played in the NFL. He felt his football career was cut short by his brain injury, Bloomberg News reported.

'I was shocked' says tourist after deadly NYC office shooting. – Reuters

Blackstone also has its headquarters in the tower, and confirmed one of the private equity firm's executives was among those Tamura killed, while others were injured and taken to hospital.

"Words cannot express the devastation we feel," the company said in a statement.

Tamura also killed a New York Police Department officer, Didarul Islam, 36, who came from Bangladesh and had been on the force three years, the mayor said. He was married with two young boys, and his wife is pregnant with their third child.

"He was doing the job that we asked him to do. He put himself in harm's way. He made the ultimate sacrifice. He died as he lived: a hero," New York Police Commissioner Jessica Tisch said.

NFL Commissioner Roger Goodell called it an "an unspeakable act of violence in our building," saying he was deeply grateful to the law enforcement officers who responded and the officer who gave his life to protect others.

Goodell said in a memo to staff that a league employee was seriously injured in the attack and was hospitalized in stable condition.

Goodell wrote there would be "increased security presence" at the league's offices "in the days and weeks to come," ESPN reported.

'He died as he lived. A hero' - New York City Police Commissioner Jessica Tisch. - AP 

Authorities offered few details about the three other victims besides the police officer – two men and a woman. A third man was gravely wounded by the gunfire and was "fighting for his life" in a nearby hospital, the mayor said.

The shooting happened along Park Avenue, one the country's most recognized streets, and just blocks from Grand Central Terminal and Rockefeller Center. 

US President Donald Trump said that he knows that area of Manhattan well.

Gunman dead following deadly shooting in New York. – AP

"I trust our Law Enforcement Agencies to get to the bottom of why this crazed lunatic committed such a senseless act of violence. My heart is with the families of the four people who were killed, including the NYPD Officer, who made the ultimate sacrifice," Trump posted on social media.

Witness Jessica Chen told ABC News she was watching a presentation with dozens of other people on the second floor of the building when she “heard multiple shots go off in quick succession from the first floor”.

She and others ran into a conference room and barricaded tables against the door.

“We were honestly really, really scared,” she said, adding that she texted her parents to tell them she loved them.

Tamura appeared to have driven to New York City from Las Vegas over three days and to have acted alone. He entered the skyscraper's lobby, turned to his right and immediately shot the NYPD officer, who was assigned to the building's security detail, Tisch said. 

She said Tamura used an M4 Carbine, a semi-automatic rifle popular with civilian US gun enthusiasts modelled on a fully automatic rifle used in the US military.

He then shot a woman and two men in the lobby but inexplicably allowed another woman to pass him unharmed before he took the elevator to the 33rd-floor offices of Rudin Management. There he fatally shot his final victim, Tisch said.

Police officers in Manhattan after the reported shooting. – Reuters

A widely circulated photo showed the permit issued to Tamura by the Las Vegas Metropolitan Police Department allowing him to legally carry a concealed firearm.

A loaded revolver was later recovered from a black BMW vehicle Tamura had left double-parked outside the office tower, along with a backpack and prescription medications, Tisch said.

One of the investigation's challenges is that Tamura only arrived in New York shortly before the shooting, leaving few clues in the area, the mayor said. Another is that for law enforcement, "dealing with those who come from areas with lax gun laws that allow individuals to have these high-powered weapons into cities like New York that have strong gun laws."