Therapies based on a hormone people make while exercising may be the next frontier in treating Alzheimer’s disease, according to a new study.
Researchers have found that the exercise-induced hormone irisin may reduce both the plaque and the tau tangles characteristic of the disease.
Before this, this same team developed the first 3D human cell culture models of Alzheimer’s disease, which it was able to use in this new research into the impact of irisin on amyloid beta in the brain.
Physical exercise had already been shown to reduce amyloid beta deposits in mouse models of Alzheimer’s, but it wasn’t clear how.
The increase of circulating levels of the muscle-derived hormone irisin through exercise regulates glucose and lipid metabolism in fat tissue. It also increases energy expenditure by accelerating the browning of white fat tissue.
Past research has shown that irisin is present in human and mouse brains. Its levels are lower in patients with Alzheimer’s.
“First, we found that irisin treatment led to a remarkable reduction of amyloid beta pathology,” said study author Se Hoon Choi, of the Genetics and Aging Research Unit at Massachusetts General Hospital in Boston.
“Second, we showed this effect of irisin was attributable to increased neprilysin activity owing to increased levels of neprilysin secreted from cells in the brain called astrocytes,” he said in a hospital news release.
Neprilysin is an enzyme that degrades amyloid beta. Elevated levels have been found in the brains of mice with Alzheimer’s that were exposed to exercise or other conditions leading to reduced amyloid beta.
Researchers were able to take this further by identifying the process that triggers cells to increase neprilysin levels.
In mice, irisin injected into the bloodstream can make its way into the brain, making it potentially useful as a therapeutic.
“Our findings indicate that irisin is a major mediator of exercise-induced increases in neprilysin levels leading to reduced amyloid beta burden, suggesting a new target pathway for therapies aimed at the prevention and treatment of Alzheimer’s disease,” said Rudolph Tanzi, a senior author of the study and director of the Genetics and Aging Research Unit.
Study findings were reported Sept. 8 in the journal Neuron.
The U.S. National Institute on Aging has more on Alzheimer’s disease.
SOURCE: Massachusetts General Hospital, news release, Sept. 8, 2023
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