Irisin, a muscle-derived hormone, reduces amyloid beta pathology, a key hallmark of Alzheimer's disease (AD), in cell models. Researchers say the findings may pave the way for new treatments for AD. The corresponding study was published in Neuron.
The amyloid cascade hypothesis suggests that the build-up of amyloid-beta proteins in the brain plays a key role in the development of AD. Therapeutics that can reduce amyloid beta accumulation are thus under investigation to treat the condition.
Studies show that physical exercise reduces various aspects of AD pathology in animals, such as cerebral amyloid beta levels, amyloid deposition, and neuroinflammation. How exactly exercise reduces amyloid beta, however, has remained unclear.
Exercise increases levels of irisin, which regulates glucose and lipid metabolism in fat tissue and increases energy expenditure by accelerating the browning of white fat tissue. Research shows both human and mouse brains contain irisin and that humans with AD and mouse models of the condition have lower levels of the hormone than healthy counterparts.
In the current study, researchers set out to determine whether irisin may explain the link between exercise and reduced amyloid beta pathology. To do so, they administered the hormone to a 3D cell culture model of AD and observed its effects.
Ultimately, they found that irisin reduced amyloid beta pathology in their cell models and increased neprilysin activity. Neprolysin is an amyloid beta-degrading enzyme that becomes elevated in mouse brains with AD following exercise or other conditions that reduce amyloid beta. The researchers further found that irisin increases neprilysin levels by binding to a receptor on astrocytes known as integrin αV/β5.
"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 AD," says Rudolph Tanzi, Ph.D., a senior author of the study and director of the Genetics and Aging Research Unit at Massachusetts General Hospital in a press release.
Sources: Science Daily, Neuron