Your brain will thank you for working up a sweat and engaging in regular exercise. But for scientists, demonstrating that physical exertion lowers the risk of Alzheimer’s isn’t enough. They want to know the mechanisms behind it.
And thanks to a brand-new study, they’ve found a “magic bullet” that could potentially be put into a pill one day to save your brain; no sweat required.
Here’s what you need to know…
Research has long shown that regular exercise is great for your brain and diminishes various aspects of Alzheimer’s pathology.
In rodents, for example, exercise reduces amyloid beta plaque formation and neuroinflammation, resulting in improved cognition. Why this is so has remained unclear until recently, when researchers discovered that an enzyme called neprilysin degrades amyloid and is elevated in the brains of mice who exercise.
In addition, as we reported in 2019, a hormone called irisin – released from muscles during exercise – is found in very low levels in the hippocampus and cerebrospinal fluid (CSF) of people who die of Alzheimer’s. Furthermore, irisin in the CSF correlates positively with levels of amyloid in the CSF and how well Alzheimer’s patients perform in cognitive tests. In other words, Alzheimer’s patients who perform well on cognitive tests have lower levels of amyloid and higher levels of irisin.
A New Model of Alzheimer’s
The accumulating evidence from mice and human studies is persuasive but circumstantial. Could scientists show irisin plays a causal role in the production of amyloid plaques and tau tangles – the hallmarks of Alzheimer’s disease?
Since the brains of living people can’t be experimented on, scientists usually use mouse models of Alzheimer’s, but these fall short of replicating exactly what occurs in humans.
To overcome this, Harvard neuroscientists developed a three-dimensional human neural cell culture model of the disease almost a decade ago. The model has proved itself to be robust in replicating the growth of both amyloid plaque and tau tangles—both of which can be hallmarks of Alzheimer’s disease.
In their latest study, published in the journal Neuron in September, they used their model to see if irisin could shed any new light on the Alzheimer’s disease process that chokes the life out of once sharp memories. Joint senior author Se Hoon Choi explains what happened.
Three Key Discoveries
“First, we found that irisin treatment led to a remarkable reduction of amyloid beta pathology. 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.”
To put that in layman’s terms Professor Hoon Choi and his team found that irisin does reduce the formation of amyloid plaques. What’s more, it was that new enzyme, neprilysin, that triggered irisin to do its good work.
Professor Hoon Choi’s team also identified the receptor that irisin binds to on astrocytes (cells) called integrin αV/β5 which is also involved in the process. This is what triggers the cells to increase neprilysin levels in the first place.
Even more exciting are the findings on irisin studied in laboratory animals. As mice research has shown, irisin injected into the bloodstream finds its way into the brain so it could potentially be utilized as a therapeutic agent. And of course, scientists will no doubt explore irisin in pill form.
Irisin: The Future of Alzheimer’s
Dr. Rudolph Tanzi, a leading Alzheimer’s scientist, joint senior author of the new study, and one of Time magazine’s most influential people in the world in 2015, believes irisin is part of the cure for Alzheimer’s disease. Dr. Tanzi explained, saying, “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.”
Of course, lots more research is needed before those therapies can be developed. However, exercise is free, safe, and readily available.
So, if you’ve been putting off giving your muscles a regular workout, this study should give you the encouragement you need to get started.
The Awakening From Alzheimer’s Team