Scientists find key to reduce risk of Alzheimer’s by 70 per cent

A super gene that may reduce the risk of developing Alzheimer’s disease by as much as 70 per cent has been uncovered by scientists. Here’s what it could mean for treatment.

A super gene that may lower the risk of developing Alzheimer’s disease (AD) by as much as 70 per cent has been identified by US researchers, who say it could take treatment in a whole new direction.

The team from Columbia University says the protective variant, which appears to allow toxic forms of amyloid out of the brain and through the blood-brain barrier, supports evidence that the brain’s blood vessels play a large role in AD.

More than 472,000 Australians live with dementia and AD.

Researchers hope the discovery of the super gene can lead to new drugs and treatments for Alzheimer’s disease. Picture: iStock

Columbia University said in a statement that the protective variant identified occurs in a gene that makes fibronectin, a component of the blood-brain barrier, which is a lining surrounding the brain’s blood vessels that controls the movement of substances in and out of the brain.

Study co-lead Caghan Kizil said AD may start with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear.

Associate Professor Kizil is from the Taub Institute at Columbia University and the research was published in April in the journal Acta Neuropathologica.

The team identified that fibronectin, which is usually found in the blood-brain barrier in tiny amounts, is in larger amounts in people who do have AD.

“Our findings suggest … that we may be able to develop new types of therapies that mimic the gene’s protective effect to prevent or treat the disease,” he said.

“It’s a classic case of too much of a good thing,” Prof Kizil says. “It made us think that excess fibronectin could be preventing the clearance of amyloid deposits from the brain.”

A world-renowned expert in Alzheimer’s and neurodegenerative diseases research, Professor Colin Masters from The Florey in Melbourne, says the research is promising, but cautions it is still “years away” from delivering new drugs.

Scans showing a ‘normal’ brain and one with Alzheimer’s disease. Picture: Supplied

While he was not involved in this research, he has studied the role of amyloid and its role in AD for more than 40 years.

Prof Masters said this research was on the right pathway. “Anything that targets amyloid is very interesting and worth exploring.”

Professor Christopher Rowe, the director of the Australian Dementia Network at the University of Melbourne and Florey Institute agreed it was exciting to find new gene variants that reduce the risk of developing Alzheimer’s disease, the most common cause of dementia in Australia.

“Genes make proteins and a small variation in a gene can lead to greater or lower production of a particular protein,” he said. “Once we have identified what the effect of a gene variant is on the particular protein, and in this case it is fibronectin and the variant reduces production, we can make drugs to either directly remove the protein, or can turn down the production by cells using new mRNA technology.

“mRNA based therapeutics for dementia are being developed including in Melbourne at the Florey Institute by a team lead by Dr Rebecca Nisbet as part of the Dementia Mission to find new treatments for this devastating disease.”

Prof Rowe said although amyloid antibody treatment for AD may soon be available in Australia, the benefit is slowing of disease progression and this is largely restricted to those with very mild symptoms of AD.

“More treatments and better tests for very early detection of AD are urgently needed,” he said.

The Columbia university team wrote the risk of developing AD significantly increases in people carrying the APOE4 gene.

Researcher Dr Rebecca Nisbet from The Florey. Picture: Supplied

They set out to test the theory that in people with the APOE4 gene who did not develop dementia, the umbrella term for the brain disease, they might carry this genetic variant that provides protection.

In pre-clinical trials the team found reducing this variant increased amyloid clearance and improved other damage caused by AD. They wrote it gave them the idea that targeting fibronectin and mimicking the protective variant could provide a strong defence against the disease.

“There’s a significant difference in fibronectin levels in the blood-brain barrier between cognitively healthy individuals and those with AD, independent of their APOEe4 status,” Professor Kizil said in the statement.

“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition.”

Co-study lead and chair of neurology at Columbia, Richard Mayeax, said the newest treatments for AD target the amyloid deposits directly and were very efficient at removing the deposits via the immune system.

“However, simply removing the deposits this way doesn’t improve symptoms or repair other damage,” Professor Mayeax said.

“We may need to start clearing amyloid much earlier and we think that can be done through the bloodstream. That’s why we are excited about the discovery of this variant in fibronectin, which may be a good target for drug development.”