September 20, 2023
Regular exercise has been linked to a range of benefits for the body, including the brain. Middle-aged people who are physically fit, for example, have a lower risk of developing Alzheimer’s disease in old age. And staying physically active may delay the onset of Alzheimer’s and slow decline in those who already have the disease.
Now scientists are getting closer to understanding why exercise may benefit the brain. Using a three-dimensional cell model, researchers at Massachusetts General Hospital in Boston found that a hormone called irisin that is produced in muscles during exercise reduces the telltale plaques and tangles that build up in the brains of those with Alzheimer’s disease. It does this by raising levels of an enzyme produced in the brain, called neprilysin, that degrades the toxic beta-amyloid that clumps together in the brain to form plaques.
The study was performed in a lab and has not been tested in people. But humans and other mammals produce irisin, and earlier studies in mice that have been bred to develop a disease resembling Alzheimer’s have shown that the hormone has memory enhancing effects and may delay the onset of dementia. The findings suggest that boosting levels of irisin in people could lead to new therapies to treat Alzheimer’s disease down the road.
“Our findings indicate that irisin is a major mediator of exercise-induced increases in neprilysin levels, leading to reduced amyloid beta burden,” said Rudolph Tanzi, the study’s senior author and director of the Genetics and Aging Research Unit at Mass General. The findings suggest “a new target pathway for therapies aimed at the prevention and treatment of Alzheimer’s disease.” The findings were published in the journal Neuron.
Irisin, named for the goddess Iris who was the messenger of the gods in Greek mythology, was discovered in 2012. The hormone, produced by the muscles when we exercise, jump-starts a cascade of chemical reactions that promote energy metabolism throughout the body. Irisin is also present in the brain. Scientists have found that levels of the hormone were especially high in the brains of people who were free of dementia when they died. But irisin was barely detectable in the brains of people who had died with Alzheimer’s disease.
The findings add to growing evidence that boosting levels of irisin with exercise may play a key role in promoting brain health and protecting against dementia. Scientists continue to study the hormone’s effects on the brain, including testing pharmaceutical forms of irisin as a treatment for dementia in animal models and, eventually, people, especially those who have lost the ability to exercise.
Exercise has other benefits as well, such as promoting bone and muscle strength and thereby lowering the risk of falls. Falls are a leading cause of death and disability, including among those with Alzheimer’s disease. Earlier research has shown, for example, that a home exercise program can provide a cost-effective solution for improving the physical frailty that often arises in those with Alzheimer’s disease. Getting regular exercise also led to modest improvements in day-to-day activities like getting dressed, walking and eating. Any improvements in these activities can allow people with Alzheimer’s to remain at home longer and delay the need to enter a nursing home.
Alzheimer’s is a complex disease that likely depends on many factors, including the genes you inherit. Lifestyle factors are likely just one part of the preventive puzzle. While regular visits to the gym or a home exercise program won’t guarantee a physically and mentally robust old age, it may help you to look, feel and act younger.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Eric Schmidt, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: Eunhee Kim, Hyeonwoo Kim, Mark P. Jedrychowski, et al: “Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling.” Neuron, September 8, 2023