An accumulation of amyloid plaques is believed to underlie Alzheimer’s disease. And researchers have now found a method to get rid of those toxic proteins.
Since the 1990s, scientific studies on Alzheimer’s disease have focused on amyloid beta proteins. Scientists suspect that the accumulation of these toxic proteins is the cause of the disease that claims more and more victims. They would therefore like to know how these proteins can be broken down in the brain. And in a new study researchers describe how.
Amyloid beta proteins
Despite decades of research, it’s still not clear exactly how Alzheimer’s disease develops. However, according to many, it seems that amyloid beta proteins have a finger in the pie. “It is generally believed that the excessive accumulation of neurotoxic amyloid-beta is the primary factor in the onset and development of Alzheimer’s disease,” said researcher Rui Zhang. Scientias.nl. “The continuous production and deposition of this protein in the brain can lead to inflammation and neuronal cell death.”
Alois Alzheimer
The idea that amyloid plaques cause the cognitive problems associated with Alzheimer’s disease arose more than 100 years ago. Then psychiatrist and researcher Alois Alzheimer described the remarkable illness of a 50-year-old woman; the woman suffered from memory loss, hallucinations and confusion. And those problems only got bigger as time went on. After the woman’s death, Alzheimer’s studied her brain and discovered something remarkable: plaques. The idea that this was the basis of her disease – which was later named Alzheimer’s by the discoverer – was born.
The amyloid beta protein has certain functions in the brain that it normally performs in a soluble form—that is, in a form that is soluble in water. But sometimes the protein also hardens and clumps together. Then it forms the many well-known amyloid plaques. High levels of such plaques in mice are known to lead to neurodegeneration and cognitive symptoms reminiscent of Alzheimer’s disease in humans. So suppose amyloid beta does indeed play an important role in Alzheimer’s disease. So how can we reduce the production of these toxic proteins or improve drainage?
Transport of macrophages to the brain
Zhang and his colleagues have now found a possible way to get rid of amyloid beta. This is done by ensuring that macrophages (white blood cells whose job it is to detect and engulf all material that could pose a threat to our health) enter the brain. The overall mechanism behind this is somewhat complex. But the bottom line is that researchers were trying to knock out a certain enzyme, METTL3, which causes important immune cells to migrate to the brain.
The enzyme METTL3
Next, the researchers wanted to see whether a lack of this enzyme in so-called myeloid cells (immature cells that normally develop into mature red blood cells, white blood cells or platelets) had any effect on the cognition of mice with Alzheimer’s disease. They found that this was the case: Treated mice performed better on several cognitive tests. This effect could then be inhibited if they blocked the migration of myeloid cells into the brain. In short, “In our study, we found that amyloid beta can be reduced in mouse brains when METTL3 is turned off,” said Zhang. This, in turn, promotes the movement of myeloid cells into the brain, followed by maturation into macrophages. These, in turn, clear amyloid beta, leading to the improved cognition in the mice.
Medicines
With their study, the researchers show a possible new way in which Alzheimer’s disease will become more treatable in the future. This may even pave the way to the development of effective drugs that inhibit the expression of METTL3. This could possibly lead to improved memory and daily functioning, although many more studies are needed to investigate this further. In any case, Zhang is optimistic. “Our developed inhibitors still need to be thoroughly investigated in a series of preclinical and clinical studies,” says the researcher. “But I believe such drugs will be approved in the future.”
End of Alzheimer’s?
But will Alzheimer’s ever completely disappear? “I don’t think so,” argues Zhang. “It is simply linked to ageing. And with people living longer and longer, I think the prevalence will continue to increase – despite all the prevention strategies that are widely adopted.”
Soften
Despite the fact that the disease may never be completely eradicated, this study also shows that efforts are being made to at least mitigate the disease. For example, further studies may ensure that the disease occurs less often, shifts to a later age or, for example, progresses more slowly so that health deteriorates less quickly. But there is not only a role for scientists in this. For example, it is thought that up to 30 percent of dementia cases could be prevented if we all lived healthier lives. For example, a 2021 study showed that a Mediterranean diet reduces the risk of Alzheimer’s disease. Eating a lot of fish, vegetables and nuts appears to protect the brain against the build-up of amyloid beta proteins. It shows that the food you consume has a major impact on your brain health.
All in all, the researchers show with their study that our fight against Alzheimer’s is far from lost. Whether this is the solution we hope for remains to be seen. But the fact that scientists now have an idea of how to break down toxic amyloid-beta proteins in the brain is an important advance that brings treatment for the disease one step closer.
