The discovery is the first time Chronic Traumatic Encephalopathy - or CTE - has been identified in an NRL athlete.

CTE is a degenerative brain disease that has been found in former players of American football, ice hockey, soccer, rugby union and others exposed to repeated head injury.

Researchers and clinicians from Royal Prince Alfred Hospital, NSW Health and the University of Sydney's Brain and Mind Centre made the discovery in two donated brains from middle-aged former professionals who played more than 150 NRL games over many years.

Their identities have been kept confidential.

Lead author Associate Professor Michael Buckland said the changes in the two brains were "distinctive and definitive".

"I have looked at about 1000 brains over the last 10 years, and I have not seen this sort of pathology in any other case before," he said in a statement on Thursday.

"The fact that we have now seen these changes in former rugby league players indicates that they, and likely other Australian collision sports players, are not immune to CTE, a disease that has gained such high profile in the United States."

Former Manly rugby union player Barry "Tizza" Taylor is the only other case of CTE identified in an Australian sportsperson.

The disease, originally called punch-drunk syndrome to describe the plight of ex-boxers, can often lead to depression and other behavioural disturbances in younger people.

Symptoms in older people, however, may be indistinguishable from Alzheimer's disease. It can only be diagnosed confidently by examination of the brain after death.

The only known risk factor for CTE is repeated concussions and blows that don't cause signs or symptoms.

The head of the Concussion Legacy Foundation in Boston labelled the Australian research - published in the international journal Acta Neuropathologica Communications on Thursday - a "groundbreaking" discovery.

"We hope the first proof of CTE in rugby league inspires the Australian scientific community to mobilise in the fight against CTE, and advances the conversation on reforms to sport that can prevent this disease," Dr Christopher Nowinski said.

It's estimated there is one concussion every 3.35 games of professional rugby league - but that rate may be significantly higher in youth competitions, the study noted.

"Given that brain autopsy is rarely pursued these days, even in cases of suicide referred to the coroner, it is difficult to assess whether these two CTE cases are serendipitous findings, or emblematic of a more common issue with rugby league and other Australian football codes," the paper said.

More than 80 athletes have pledged to donate their brains to the Australian Sports Brain Bank, set up by Associate Professor Buckland in 2018.

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Australian Associated Press