Exercise-induced hormone irisin may reduce effects of Alzheimer’s disease

BOSTON – Researchers who previously developed the first 3D human cell culture models of Alzheimer’s disease have now used their model to investigate whether the exercise-induced muscle hormone irisin affects amyloid beta pathology.

The initial model displayed two major hallmarks of the condition, the generation of amyloid beta deposits followed by tau tangles, the press release explained.

As reported in the journal Neuron, Massachusetts General Hospital led a team which uncovered promising results suggesting that irisin-based therapies might help combat Alzheimer’s.

Physical exercise has been shown to reduce amyloid beta deposits in various mouse models of AD, but the mechanisms involved have remained a mystery, the press release noted.

Exercise increases circulating levels of the muscle-derived hormone irisin, which regulates glucose and lipid metabolism in fat tissue. It also increases energy expenditure by accelerating the browning of white fat tissue.

Studies have revealed that irisin is present in human and mouse brains and that its levels are reduced in patients with Alzheimer’s and in mouse models of the condition.

To test whether irisin plays a causal role in the link between exercise and reduced amyloid beta, Dr. Se Hoon Choi and Dr. Eun Hee Kim, of the Genetics and Aging Research Unit at Massachusetts General, along with additional research colleagues, applied the hormone to their 3D cell culture model of Alzheimer’s disease.

“First, we found that irisin treatment led to a remarkable reduction of amyloid beta pathology,” said Choi. “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.”

Neprilysin is an amyloid beta–degrading enzyme that has been found to be elevated in the brains of mice with Alzheimer’s that were exposed to exercise or other conditions leading to reduced amyloid beta, he noted.

Previous studies with mice showed risin injected into the blood stream 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,” said Dr. Rudolph Tanzi, a senior author of the study and director of the Genetics and Aging Research Unit. ”That suggests a new target pathway for therapies aimed at the prevention and treatment of Alzheimer’s disease.”

The bottom line is that more exercise has been proven to influence the hormones, enzymes and proteins which work to combat the effects of Alzheimer’s disease.

Science-minded people can read the study results at Neuron.