The brain is a carefully fortified fortress. Along a total of 600 km long blood vessels stands a defensive wall called the blood/brain wall. It is made of three cell layers and it is next to impossible to get through it. Only oxygen, nutrition and a few other substances are allowed to leave the blood and reach the cells of the brain. Bacteria and viruses are kept away with great determination.
In rare cases, microbes manage to enter the brain, but they immediately encounter the brain’s defenses, immune cells called microglia. These cells recognize the invading microbes, engulf them and break them down.
But if the microbes are too many, the brain has one defense left. The neurons release the substance beta-amyloid, which wraps around the microbes and kills them.
Protein stifles invasion
The substance beta-amyloid has been known for decades as a disease-causing scourge. Now scientists have discovered that the substance is actually an important part of the brain’s defenses against microbes.
The brain’s defense mechanism ensures the best possible protection for vulnerable neurons. But even the best defenses are not always enough. The invader can gain a foothold in the brain, poison it, and turn the brain’s very arsenal against itself. The result is that the brain tissue gradually breaks down.
An experiment conducted in 2019 showed that this is exactly what happens in the brains of Alzheimer’s patients. Furthermore, it was possible to identify the invading bacteria, which turned out to be the bacteria that causes gingivitis. For the taste, there is now a drug on the way that for the first time should be able to stop the progress of this malignant disease.
The ongoing search for the cause of Alzheimer’s
More than 30 million people suffer from Alzheimer’s worldwide, and that number is expected to triple in a few decades in line with increasing age. There is currently no cure and no medication that can stop the progression of the disease.
Alzheimer’s affects memory and problem-solving skills, and the disease can also change mood and personality. Usually, the first symptoms do not appear until after sixty, but it is possible for much younger people to get the disease.
Video: This is how Alzheimer’s destroys the brain
For decades, scientists have studied the disease and they have answered many questions. First, brain scans show that many areas of the brain have shrunk compared to what is normal – especially the brain, which plays a major role in memory.
Secondly, the disease is related to changes in the proteins of the brain. Early in the disease process, the so-called toe protein begins to fold in the neurons.
The toe protein is an important part of the skeletal system of the cells and when it is deformed, it destroys the structural layer of the cells and at the same time their ability to exchange nerve signals. Eventually these cells die.
Another protein, beta-amyloid, also plays a major role. In general, the brain cells only release very little of this substance, and that amount is simply cleaned away with other impurities while people sleep. In Alzheimer’s patients, however, you can find a lot of the substance and it clumps together in so-called plaques, which are dangerous for the neurons.
The big question is now what caused this, and scientists have now probably found the answer.
The brain is damaged in self-defense
The link between beta-amyloid and Alzheimer’s has been known since the 1980s. Since then, scientists have tried to understand the role of the protein in order to gain an understanding of what triggers this massive accumulation. But it wasn’t until the last few years that people came close to solving that riddle.
In 2010, American and Swedish researchers showed that beta-amyloid stops the growth of both bacteria and fungi in petri dishes. A few years later, it was discovered that the protein also inhibits the ability of both influenza and herpes viruses to infect cells.
And in 2016, American and Australian scientists were able to show that in mouse brains, bacteria cause the release of beta-amyloid and that the substance binds to the bacteria. Taken together, the results show that the protein plays an important role in protecting the brain against microbes.
The role of beta-amyloid may at best have lifted the veil on the cause of Alzheimer’s. Many scientists now believe that the accumulation of the protein in the brain is a direct result of a bacterial or viral invasion of the brain.
The invasion prompts the neurons to release beta-amyloid in self-defense, but if the invasion continues for years, the protein builds up and begins to cause damage to the brain itself.
The discovery coincides with previous studies, where it has been found that infection with the herpes virus increases the risk of developing Alzheimer’s in people with a mutation in the gene APOE – a gene that plays an important role in the immune system’s fight against microbes – and that there are many of this virus in the plaques that beta-amyloid forms in the brains of Alzheimer’s patients.
And in 2019 came another great discovery. A multinational team of scientists, led by the American doctor Stephen Dominy, managed to map in detail the entire path from infection to Alzheimer’s disease in mice.
But they didn’t focus on the herpes virus. Instead, they found another microbe that was clearly linked to Alzheimer’s – a bacterium that usually attacks the gums.
The bacteria kills nerve cells
Porphyromonas gingivalis – this little bacterium could soon become enemy number one in scientists’ fight against Alzheimer’s. The bacterium has been known for a long time, because it is one of the main causes of gingivitis, an infection that up to half of the world’s population has to deal with. The bacteria is also present in the mouth of about 25% of people without gingivitis.
A correlation between gingivitis and Alzheimer’s has previously been found. In a study from 2017, it was found that persistent gingivitis can increase the risk of Alzheimer’s by 70%, but the other has not been proven; that inflammation is the direct cause of Alzheimer’s.
But Stephen Dominy and his colleagues have now succeeded.
The team first discovered that brains from Alzheimer’s patients had significantly more of the toxin of the gum bacteria called “gingipain” than brains from healthy people. However, these substances were also found in the healthy brains, but in much smaller amounts.
Upon closer inspection, the researchers saw that the gingipain substances were, among other things, in the memory center of the dragon and the cerebral cortex, and their concentration was high where plaques of toe protein and beta-amyloid had formed.
The toxins destroyed healthy toe proteins that characterize one of the early stages of Alzheimer’s development. The poison also killed neurons, both in petri dishes and in the brains of mice.
The scientists now put the bacteria in the mouths of mice and discovered that it reached the brain in six weeks. There it resulted in the accumulation of beta-amyloid and the loss of neurons in the dragon.
Gum bacteria attacks the brain
The bacteria that cause gingivitis can enter the brain and when it does, it can seriously damage the brain cells.
The bacteria is transmitted from the mouth
The bacterium Porphyromonas gingivalis produces the toxin gingipain. Some toxin molecules sit on the surface of the bacteria, while others are distributed throughout the environment. These are enzymes that can break down tissue and damage the gums. Weakened gums open a path into the bloodstream and the bacteria can be spread throughout the body.
The poison damages the structure of the nerve cell
The bacterium enters the brain and the toxins attack nerve cells where they break down the toe protein inside the cells. The toe proteins keep the cell’s framework stable and without them the cell deforms and the ability to communicate disappears. Eventually, the neurons die.
Taken together, these findings demonstrate the best-substantiated link to date between microbial attack and the development of Alzheimer’s.
Dominy and colleagues have already gone one step further and developed a substance that is able to inhibit the toxins and kill the bacteria.
New material tested on patients
In their search for a cure for Alzheimer’s, scientists have focused on beta-amyloid for decades.
In 2002, an experiment was conducted with a vaccine that was supposed to get the patient’s immune system to attack the accumulation of beta-amyloid. That experiment had to be stopped because of serious side effects.
The same thing happened in 2011 when a substance that inhibits the formation of beta-amyloid was tested. Other attempts to attack this protein have also failed as they did not have the desired effect.
Scientists have not yet released their ideas for attacking this protein, but many now consider it a wrong strategy.
A growing number of discoveries showing a connection between microbes and Alzheimer’s are now focusing more on microbes, and Stephen Dominy and his group are at the forefront.
The group has developed the substance COR388, which binds to the toxins of the periodontal bacteria and deactivates them.
The group’s experiments show that substances similar to COR388 prevent the bacterium from killing neurons in petri dishes, and the substances inhibit the growth of the bacterium – probably because the bacterium uses the toxins to break down its own food. If the toxins are deactivated, the bacteria cannot spread from the mouth to the brain.
In mice with infected brains, COR388 and similar substances reduced the number of bacteria in the brain, prevented the loss of neurons in the dragon and slowed the accumulation of beta-amyloid.
Therefore, it is far from solving all Alzheimer’s puzzles, but this discovery gives reason for optimism. COR388 has been shown to have no serious side effects in humans and is currently being tested on more than 500 Alzheimer’s patients.
