Scientists have identified new genetic factors of Alzheimer's disease
Alzheimer's disease remains one of the main causes of dementia, but the mechanisms of its development are still not fully understood. Genetic features can affect the likelihood of developing the disease, but scientists continue to look for specific DNA regions and cellular processes associated with its development. An international team of researchers conducted a large-scale analysis of genetic data and discovered dozens of previously unknown risk factors. The information about the role of immune and nerve cells in the brain is provided in the Izvestia article.
48 new DNA sites
The results of the study are published in the journal Nature. An international team led by scientists from the University of Oslo and the University Hospital of Oslo combined data from 30 research groups. In total, the analysis covered about 2.8 million people, including 183,620 people with Alzheimer's disease.
Alzheimer's disease is a progressive neurodegenerative disease in which the nerve cells of the brain are gradually destroyed and the connections between them are disrupted. It is the most common cause of dementia and is usually manifested by memory impairment, impaired thinking, speech, and the ability to navigate in space. As the disease develops, it becomes increasingly difficult for a person to perform daily tasks on their own.
The researchers found 127 DNA regions statistically associated with the risk of developing the disease. Of these, 48 had not previously been identified in such genetic studies. Scientists have also identified genes that may be involved in the development of the disease, and identified several biological processes that deserve further study.
The authors note that the identified regions should not be considered separate genes, each of which independently causes the disease. We are talking about genetic areas where statistical links with the risk of disease have been found. Additional experiments will be required to determine which genes and mechanisms are responsible for these connections.
The brain's immunity is under suspicion
One of the main results was the confirmation of the role of microglia, immune cells of the central nervous system. They are involved in the removal of damaged cellular structures and potentially harmful substances, helping to maintain the normal functioning of the nervous tissue.
Genetic analysis revealed links with the processes of microglia activation, immune cell recruitment, and removal of cellular material. Scientists have also discovered genetic signals related to the processing of amyloid— a protein that can accumulate in the brain in Alzheimer's disease.
In addition, the researchers found a connection with the activity of astrocytes, auxiliary cells of the nervous tissue involved in maintaining the functioning of neurons. Another group of genetic signals turned out to be associated with the preservation of the protective membrane around nerve fibers. It helps to isolate them and ensures the normal transmission of nerve impulses.
Thus, the results indicate the involvement of several interrelated processes: immune activity, protein processing, and maintaining the structure of nervous tissue. However, the discovered genetic links alone do not prove that each of these processes directly triggers the disease.
Scientists have found vulnerable neurons
The study revealed genetic signals associated not only with immune cells, but also with certain types of neurons. In particular, the scientists identified three groups of nerve cells: Sncg, Sst and L6 IT Car3. For two of them, Sncg and Sst, previous work has already indicated vulnerability in the early stages of Alzheimer's disease.
The authors also compared the activity of genes in the brain cells of people with and without the disease. It turned out that genes whose activity is increased in microglia and decreased in neurons in Alzheimer's disease are more often associated with genetic risk factors. This indicates a possible link between increased immune processes and impaired nerve cell function.
According to the researchers, the results help to determine more precisely which cell types and biological mechanisms should be studied. Previously, genetic work had already pointed out the importance of microglia, but the new map allowed us to take a closer look at the involvement of individual groups of neurons.
The genetic risk was higher
Another result was a new assessment of the contribution of common genetic variants to differences in the risk of Alzheimer's disease between people. For participants of European origin, the researchers estimated this figure at about 16%. Previous estimates were about 5%.
The difference is due, among other things, to the use of a statistical method that more accurately takes into account the influence of the APOE gene. Its variant APOE-e4 has long been known as one of the most significant genetic risk factors for Alzheimer's disease. The authors of the study believe that common genetic variants together may play a more significant role than previously thought.
Alexey Shadrin, researcher
This shows that there is still more to be discovered in large-scale genetic research than some had assumed. But this is an indicator at the population level. This does not mean that 16% of Alzheimer's cases in any person are caused by their genes, and it does not mean that a genetic test can determine whether a person will develop this disease. Age, environment, and other biological and personal factors also play an important role.
Scientists have also improved models for predicting genetic risk, but so far they are considered primarily as a research tool. The new data will help create laboratory models of the disease and select biological mechanisms for further study. But before using the discovered links to develop treatment methods, it is necessary to establish which of them are really causal and whether it is safe to influence the relevant processes.
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