Gene mutation that ‘reduces odds of Alzheimer’s disease by 70%’ discovered

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A gene mutation that reduces the odds of developing Alzheimer’s disease by 70% has been discovered by scientists.

This “protective” variant occurs in a gene – FN1 – which makes a protein known as fibronectin.

The discovery was made in people who had another gene known as APOEe4, which significantly increases the risk of developing Alzheimer’s.

The researchers said their findings, published in the journal Acta Neuropathologica, could lead to new types of therapies or drugs that could “mimic the gene’s protective effect” to prevent or treat the disease.

Fibronectin is usually present in the blood-brain barrier – a lining that controls the movement of substances in and out of the brain – in small amounts and plays a key role in wound healing and tissue repair.

However, it exists in larger quantities in people with Alzheimer’s and it is thought that having excess fibronectin prevents the brain from clearing another protein known as amyloid, which sticks together and later becomes plaque in the brain that damage cells.

The eventual death of these brain cells is what leads to Alzheimer’s.

Researchers have found the FN1 variant prevents the build-up of excess fibronectin at the blood-brain barrier, thus seemingly protecting against the disease.

Dr Richard Mayeux, the Gertrude H Sergievsky professor of Neurology, Psychiatry, and Epidemiology at Columbia University in New York City, said: “These results gave us the idea that a therapy targeting fibronectin and mimicking the protective variant could provide a strong defence against the disease in people.”

The researchers said that while some new treatments for Alzheimer’s can target the amyloid deposits directly, simply removing the deposits does not improve symptoms or repair other damage.

Dr Mayeux 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.”

Combining data from 11,000 participants, the researchers calculated that FN1 mutation reduces the odds of developing Alzheimer’s in APOEe4 carriers by 71%.

It also stalls the disease by roughly four years in those who eventually develop Alzheimer’s, the team said.

The FN1 variant could also protect against Alzheimer’s disease in people with other forms of the APOE gene, the scientists added.

Dr Caghan Kizil, an associate professor of neurological sciences at Columbia University Vagelos College of Physicians and Surgeons, said: “There’s a significant difference in fibronectin levels in the blood-brain barrier between cognitively healthy individuals and those with Alzheimer’s disease, independent of their APOEe4 status.

“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.”