Alzheimer's: Exercise-induced hormone may help reduce plaque

Evan Walker
Evan Walker TheMediTary.Com |
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Weightlifting is one of the exercises recommended for brain health in older adults. Solskin/Getty Images
  • Researchers say they have found evidence that exercise helps produces a hormone called irisin that could prevent Alzheimer’s disease.
  • Irisin may enhance neprilysin, which fights the brain-damaging abnormal protein amyloid beta.
  • Previous studies have shown irisin injected into the blood stream of mice can make its way into the brain, creating a new pathway for targeted therapies.

A team led by researchers from Massachusetts General Hospital says it might have found evidence suggesting irisin-based therapies could help combat Alzheimer’s disease.

Irisin is a muscle-derived hormone that increases in the body following exercise. It regulates glucose and lipid metabolism in fat tissue and increases energy expenditure by accelerating the browning of white fat tissue.

Studies have shown irisin is present in human and mouse brains, but its levels are reduced in people with Alzheimer’s as well as in mouse models of Alzheimer’s.

The team involved in the latest study, which was published today in the journal Neuron, have previously developed the first 3D human cell culture models of Alzheimer’s disease that display two major hallmarks of the condition: the generation of amyloid beta deposits (plaques) and neurofibrillary degeneration (tangles) of the protein tau found in brain cells (neurons).

Amyloid is an abnormal protein and its presence in organs can eventually damage them.

In their new study, researchers said physical exercise has been shown to reduce amyloid beta deposits in various mouse models of Alzheimer’s, but the mechanisms involved have remained a mystery.

They used the same model to investigate whether exercise-induced increased levels of irisin affects amyloid beta pathology.

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

“First, we found that irisin treatment led to a remarkable reduction of amyloid beta pathology,” said Choi in a press release. “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 is elevated in the brains of mice with Alzheimer’s that were exposed to exercise or other conditions leading to reduced amyloid beta.

The researchers uncovered more details about the mechanisms behind irisin’s link to reduced amyloid beta levels.

For example, they identified a receptor that irisin binds to, triggering the cells to increase neprilysin levels.

They also discovered irisin’s binding to this receptor causes reduced signaling of pathways involving two key proteins: extracellular signal-regulated kinase (ERK) and signal activator of transcription 3 (STAT3).

Reducing the signaling of ERK and STAT3 is critical for irisin to enhance neprilysin, which fights the brain-damaging amyloid beta.

Previous studies have shown irisin injected into the blood stream of mice can make its way into the brain, creating a new pathway for targeted therapies.

“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 at Massachusetts General.

Ryan Glatt, a senior brain Health coach and director of the FitBrain Program at Pacific Neuroscience Institute in California, told Medical News Today the research is still in the early stages and there’s much more work to be done.

“Prior studies in adult humans have demonstrated increased levels of irisin as the result of exercise, particularly resistance training, which may mediate some of the benefits of exercise on brain health,” Glatt said. “The exact mechanisms require further elucidation, so studies like these can get us closer to that understanding. More human research is needed and future studies could compare the mediating effects of irisin in comparison to other growth factors, such as insulin-like growth factor-1 (IGF-1) and brain derived neurotrophic factor (BDNF).

Glatt added that future research should also seek to clarify what modes of exercise (i.e., aerobic versus resistance training) as well as what intensities and what durations lead to in terms of the concentration of certain myokines such as irisin.

“The responses from adults who are cognitively healthy in comparison to those with existing cognitive impairment needs further research, and the cognitive outcomes as the result of the expression of myokines, such as irisin, need to be better understood,” Glatt said.

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