It is no longer a secret that sport and exercise are also good for the brain. But very few people know how far experimental Alzheimer’s research has progressed. Far away from neuroscience, in 2012 the messenger substance irisine discovered a signaling molecule secreted by muscle cells during physical activity. A decade later we know: this molecule, often crudely referred to as ‘sports hormone’, has the potential to revolutionize Alzheimer’s therapy.
One molecule, one disease, one breakthrough study
Alzheimer’s affects more than 35,000,000 brains worldwide, robbing people of their memory and therefore their personality. In countries with a high life expectancy like Germany, about every second person older than 80 years is diagnosed with Alzheimer’s. Not a good prospect for an aging society — at least until 2019, when a 25-strong research team finally studied irisin in a neuroscience lab.
In their outstanding study published in Nature Medicine was published, the team discovered evidence that irisin can be used therapeutically against Alzheimer’s disease (1). The first research question was obvious: it was known that irisin helps significantly in the release of a factor that in turn promotes learning through synapse formation and without which memory would be impossible (the brain-derived neurotrophic factor). So could it be that forgetful Alzheimer’s patients have lower irisin levels than healthy people? And indeed it was like this: in the spinal fluid (liquor) of Alzheimer’s patients, greatly reduced levels of irisin were found compared to healthy people and patients with other diseases that affect memory.
Alzheimer’s is associated with protein deposits in the brain (‘protein garbage’). Above all, the protein beta-amyloid plays a role here, especially in the areas that are crucial for memory, such as the hippocampus. The researchers now wanted to test whether the artificial addition of amyloid beta had an effect on irisin levels. They therefore removed the hippocampi from laboratory rats and treated them with beta-amyloid in a Petri dish. Here, too, an astonishing finding: after the treatment, irisin was hardly to be found on the hippocampus cells. But that was not enough for the researchers. They injected the amyloid beta into the brains of healthy mice, and the Alzheimer’s protein also reduced the irisin content in the hippocampus. So it seemed like in Alzheimer’s the beta-amyloid junk was crowding out the irisin from the brain. Consequently, the researchers next looked at genetically modified mice that develop Alzheimer’s very early and show the typical deposits. The suspicion was confirmed: these Alzheimer’s mice lacked the normal levels of irisin in the brain that healthy mice have.
At this point, other scientists would probably have stopped researching and published the results immediately – they were amazing enough. But not this team, which seemed to have taken a liking to injecting protein junk into brains: now it was the turn of living humans. Two men and three women, who all suffered from epilepsy and therefore underwent surgery, had a tiny amount of the cortex removed during the operation – with their consent, of course. This sample of healthy human brain tissue was kept alive artificially and then treated with beta-amyloid in the laboratory. The irisin of the cerebral cortex fizzled out.
Irisin: a rain jacket for the brain?
Now the researchers really wanted to know: can an irisin booster protect mice from Alzheimer’s? They injected one group of mice with an irisin booster and another group with just a similar control substance. As a result, the irisin level in the brain was greatly increased in the first group for 6 days. Now the two groups of mice were injected with the Alzheimer’s protein, beta-amyloid – with sensational results: only the second group fell ill, while the mice with the irisin booster were spared and did not show any memory problems in the tests. To be on the safe side, the experiment was repeated with the mice that developed Alzheimer’s disease at an early age. When these mice were given the irisin booster, they didn’t get sick — even though they were actually genetically engineered by humans to be sure to get Alzheimer’s. A scientific breakthrough with therapeutic potential.
The research group also successfully tested the protective effect of irisin back in the Petri dish. Hippocampal slices previously boosted with irisin no longer exhibited the abnormal changes in structure and function when subsequently treated with beta-amyloid. As if the protein waste was afraid of the irisin, it never occupied the same dendrites to which a lot of irisin previously attached itself (dendrites are something like the antennae of nerve cells). Irisin, you could say, works like a water-repellent rain jacket – just for the brain and against beta-amyloid.
As already mentioned, irisin is actually a messenger substance of our stressed muscles. As the last experiment in their large study, the scientists therefore tested whether natural irisin, which is produced through exercise, could alleviate Alzheimer’s symptoms. To do this, they divided mice into an athletic and an unsportsmanlike group. The sports group swam an hour a day for five days a week, while the non-sports group sat more. After five weeks, both groups were given an amyloid beta infusion to induce Alzheimer’s. The result: the mice in the exercise group were unremarkable in memory tests, in contrast to the unsportsmanlike mice. Irisin levels also differed as expected, increased in the athletic cohort and decreased in the non-athletic cohort.
Is Alzheimer’s now treatable?
The study results have meanwhile been repeatedly confirmed (2). They impress with the large extent to which irisin kept what the researchers’ hypotheses promised. They also suggest a real therapeutic utility of irisin, perhaps in the form of an injection (peripheral injection also increased irisin levels in the brains of the mice). But that’s still a long way off, because animal models are of course something different than clinical studies on humans. It is also still a mystery why irisin works as an antagonist of beta-amyloid at all. However, without such a well-founded knowledge of how it works, no drug will be approved. But everyone should ask themselves one question: nobody wants to get Alzheimer’s disease, and if one day the irisin drug for Alzheimer’s came along, we would all be ready to pay top dollar for it. So what’s stopping us from sticking to natural irisin and exercising a few times a week until then?
Sources:
The article is based on an earlier text by the author in the dossier of the German Journal of Sports Medicine.
(1) Lourenco MV, Frozza RL, de Freitas GB et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. nat. medication 2019; 25:165-175. doi:10.1038/s41591-018-0275-4
(2) Islam MR, Valaris S, Young, MF et al. Exercise hormone irisin is a critical regulator of cognitive function. nat. metab. 2021; 3: 1058-1070. https://doi.org/10.1038/s42255-021-00438-z