Running could keep the brain as well as the body healthy.© Getty

Exercise helps to flush a toxic molecule from the brain and causes a beneficial one to move in and protect nerve cells, research on mice shows. The discovery might help to explain why staying fit and keeping mentally active seem to fend off Alzheimer's disease in humans.

"Our experiments support the idea that exercise is a good approach to all types of problems in the brain and that a sedentary lifestyle is a risk factor," says Ignacio Torres-Aleman, who led the study at the Cajal Institute in Madrid.

Torres-Aleman and his colleagues were intrigued by previous studies showing that exercise slows mental decline in mice engineered to mimic Alzheimer's disease. They set out to discover the reason.

They found that exercise doubled the levels of a protein that helps to flush molecules thought to underlie Alzheimer's disease out of the mice's brains and into their blood. The protein, called megalin, ejects a potentially destructive protein called amyloid-beta. In Alzheimer's patients, amyloid-beta accumulates in clumps throughout the brain.

Megalin also binds to a beneficial molecule in the blood, called insulin-like growth factor, and transports it to the brain. This growth factor is perhaps best known for bulking up muscles after exercise, but it also helps to keep nerve cells healthy.

Brain boost

To reveal the tricks of megalin, the researchers manipulated levels of the protein in the brain of mice with Alzheimer's-like disease. Artificially boosting megalin partly improved mental performance, as measured in a maze test.

Levels of megalin decline with age in normal mice. The researchers suggest that this hints at a molecular link between ageing and neurodegenerative disease.

The findings appear in the Journal of Neuroscience¹. But whether they will hold true remains to be seen. Paul Adlard, a neuroscientist at the University of California, Irvine, has looked at the brains of mice in a different model of Alzheimer's disease. His data, although only preliminary, suggest that exercise does not boost levels of the protective insulin-like growth factor.

Adlard says that the findings of Torres-Aleman and his colleagues are "tantalizing", but that more study is needed.

Bright future

Others are more optimistic. "It's a new idea," says Mark Mattson, a researcher at the National Institute on Aging in Baltimore, Maryland. The findings, he says, open the door to developing drugs that could boost levels of the megalin shuttle and help keep the brain healthy.

"It's initial data but I think it has potential to be very relevant to people," he adds.

Mattson notes that the link between exercise and brain health is still not certain in humans, although the evidence is mounting up. Other research has found that staying mentally agile or even maintaining a slim physique may help to protect against Alzheimer's and other brain disorders. 

Cajal Institute in Madrid

• References

  1. Carro E., et al. The Journal of Neuroscience, 25. 10884 - 10893 (2005).