Alzheimer's-2019
The fight against Alzheimer's disease – victories and defeats in the past year
Alzheimer's disease is responsible for 60-70% of all cases of senile dementia. The causes and mechanisms of its development are unknown for sure, and the search for ways to treat or at least slow down the pathological process has not yet yielded tangible results. However, work in this direction is going on on all fronts, and last year was no exception. In particular, we have learned that the health of our brain largely depends on ourselves
Today, most experts agree that an essential role in the development of Alzheimer's disease is played by the accumulation of improperly folded protein molecules in brain tissues: beta-amyloid, which forms intercellular amyloid plaques, and hyperphosphorylated tau protein, which forms intracellular neurofibrillary tangles. Therefore, the main therapeutic strategies are aimed at reducing pathological protein aggregates in the brain with the help of pharmacological drugs aimed at one of these proteins. However, candidate drugs have not yet proven their effectiveness in clinical trials.
An example is Aducanumab, created on the basis of monoclonal antibodies to beta-amyloid, which should recognize and bind to amyloid plaques, thereby "exposing" them to the attack of the body's immune system In 2016, researchers announced that while taking this drug, the size of amyloid plaques in the brain decreased, and a decrease in cognitive the time has slowed down. A year later, tests on a large sample showed the futility of trying to contain the growing mental deficit. And later, the developer company changed its conclusions again to more optimistic ones. Such throwing did not add confidence both to the effectiveness of the drug and to the amyloid hypothesis of the development of Alzheimer's disease, which takes into account the accumulation of only one pathological protein in the brain.
A way out of this impasse can be combinatorial therapy aimed simultaneously at beta-amyloid and tau protein. There are facts that suggest that these two abnormal proteins interact, jointly stimulating neurodegeneration. This assumption is confirmed by the amazing story of an elderly woman from a family with early hereditary Alzheimer's disease, which is caused by a mutation in one of the genes. Although the woman was a carrier of this mutation, and an unusually large number of amyloid plaques were detected in her brain, at the age of 73 she retained a sound mind and a firm memory. The reason is the absence of clusters of tau protein due to the presence of two mutant copies of another gene that promotes the penetration of this toxic protein into cells.
By the way, questionable results in the trials of aducanumab may also indicate that the treatment was started too late, when the pathological process went far. So the idea of creating a preventive vaccine based on the pathological objects themselves, rather than ready-made antibodies, arose. In this case, this means that the Alzheimer's vaccine must contain both beta-amyloid and tau proteins.
Such a combinatorial approach was tested in an experiment on a "living model" – transgenic mice, in whose brains pathological human proteins can accumulate with age. When young animals were injected with a mixture of two vaccines containing human beta-amyloid and tau protein molecules, specific antibodies began to be produced in their bodies. As the test on the brain preparations of a person with Alzheimer's disease showed, these antibodies successfully recognized amyloid plaques and neurofibrillary tangles. As for the mice themselves, such vaccination at an early age slowed down the accumulation of pathological proteins in their brains.
Unfortunately, such drugs have not yet entered medical practice. However, we can ourselves influence some of the factors contributing to the development of Alzheimer's disease. So, in 2019, the hypothesis about the participation of bacteria in this process was confirmed Porphyromonas gingivalis is the causative agent of periodontitis, an inflammatory disease of the tissues surrounding the tooth. Toxic proteins secreted by it were found in postmortem samples of brain tissue of patients, and their number was directly proportional to the amount of pathological tau protein. And although this bacterium occurs in a small amount in every fourth person, it is obvious that dental health should not be neglected.
To reduce the risk of neurodegenerative pathologies leading to dementia, other, quite ordinary measures to preserve health will also help. For example, you can simply reduce the amount of salt consumed, as it turned out that a high-salt diet contributes to the formation of clusters of pathological tau protein in the brain. Or increase physical activity, during which the regulatory protein irisin is released into the blood, which helped improve memory and learning ability in experimental mice.
And already this year, a work was published confirming that one of the risk factors for the development of Alzheimer's disease is an ordinary lack of sleep. It turned out that even one sleepless night leads to a significant increase in the blood content of one of the main markers of pathology of nervous tissue – beta-amyloid. By the way, it was previously shown that in the same situation, the amount of beta-amyloid increased, only already in the cerebrospinal fluid.
Summing up, we can say that while Alzheimer's disease has not been defeated, it remains one of the most serious threats to aging. Let's hope that biologists and doctors in the near future will be able not only to find potential ways to overcome this problem, but also to achieve more tangible results.
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