STANFORD, Calif. — A treatment that protects couch potatoes against brain diseases could be on the horizon. Scientists at the Stanford School of Medicine have identified a brain-boosting protein in the blood of extremely active mice. When they injected this substance into sedentary mice, the couch potatoes saw the same cognitive improvements.
The breakthrough opens the door to medications that reduce the risk of dementia in humans, since those who are physically inactive are most prone to the memory-robbing condition. Regular brisk walks or bike rides increase production of neurons and dampen harmful brain inflammation.
“We’ve discovered that this exercise effect can be attributed to a large extent to factors in the blood, and we can transfer that effect to a same-aged, non-exercising individual,” says senior author Professor Tony Wyss-Coay in a university release.
The team compared blood samples from fit and unfit mice of the same age. Tests showed that transfusions from the runners decreased neuro-inflammation and improved cognitive performance.
The researchers also isolated a blood protein that is key to the phenomenon. Known as clusterin, it binds to receptors on cells that line the blood vessels of the brain. These cells have been found to be inflamed in most Alzheimer’s patients, Prof. Wyss-Coray explains.
The findings, published in the journal Nature, provides new insight about the mechanism behind links between physical activity and good brain health.
Staying active can defend against dementia
Recent research has suggested that couch potatoes are just as likely to develop dementia as those carrying certain genes which increase the risk of Alzheimer’s. People over 65 who rarely exercise are among the most likely to develop the disease, even without any genetic risk factors.
Estimates show the number of dementia cases worldwide is set to triple to over 150 million by 2050 due to the aging population. With no cure in sight, there’s an increasing focus on strategies that increase levels of activity. Prof. Wyss-Coray and colleagues say clusterin is largely responsible for the benefits and can be developed into a drug.
For those who have suffered from the flu, many can relate to the loss of mental sharpness that comes from a fever-inducing infection.
“You get lethargic, you feel disconnected, your brain doesn’t work so well, you don’t remember as clearly,” Prof Wyss-Coray says.
Such illnesses result from systemic inflammation which spills into the brain. Neuro-inflammation also speeds the progression of Alzheimer’s. Earlier this year, Prof. Wyss-Coray identified signs of brain inflammation in people who had died of COVID-19.
Can a blood transfusion make you smarter?
In the new study, researchers placed running wheels in the cages of three-month-old lab rodents. That’s equivalent to a 25-year-old human. A month of steady use substantially increased the quantity of neurons and other brain cells compared to their sedentary companions.
The researchers next collected blood from both groups and injected other sedentary mice with cell-free plasma from either type. Each transfusion every three days equaled seven to eight percent of their total blood volume — about half to three-quarters of a pint in a human.
“The mice getting runner blood were smarter,” Prof. Wyss-Coray reports.
On two different lab tests of memory, sedentary mice injected with marathoner plasma outperformed those getting “couch-potato” blood transfusions. They also had more cells that give rise to new neurons in the hippocampus; the brain region which controls memory and navigation.
Scans showed roughly 2,000 genes were switched on in response to marathoner plasma. The 250 whose activation levels changed most were strongly linked to less brain inflammation.
“The runners’ blood was clearly doing something to the brain, even though it had been delivered outside the brain, systemically,” Prof. Wyss-Coray says.
So, can this treatment work in humans?
Further analysis showed removing clusterin from the runners’ plasma largely negated its anti-inflammatory effect. The protein was much more abundant in their blood than in sedentary mice. Study authors confirmed the findings through a six-month aerobic exercise program involving 20 military veterans.
All the participants had MCI (mild cognitive impairment) that can lead to full blown Alzheimer’s. They also had elevated levels of clusterin in their blood. Clusterin by itself – even though the infusions take place outside of the brain – reduced brain inflammation in two different groups of lab mice.
The mice had been genetically engineered to develop acute inflammation throughout the body or Alzheimer’s-related chronic neuro-inflammation.
Prof. Wyss-Coray believes a drug that enhances or mimics clusterin’s binding to its receptors on brain endothelial cells could slow inflammation’s ability to spark degenerative diseases in the human brain, including dementia.
South West News Service writer Mark Waghorn contributed to this report.