The influence of rs75932628 and rs2234253 polymorphisms of the TREM2 gene and the mTOR signaling pathway in the development of Alzheimer's disease

Abstract

Annotation. According to the data of the World Health Organization, as of March 15, 2023, more than 55 million cases of dementia disorders were recorded in the world. Among them, Alzheimer’s disease remains a global medical challenge, which is particularly relevant for low- and middle-income countries. This pathology already ranks 7th among the causes of death among the elderly population and has a significant social and economic impact. The purpose of the study – to determine the role of the TREM2 gene and its polymorphisms, in particular rs75932628 and rs2234253, in susceptibility to Alzheimer’s disease. To analyze the role of the mTOR signaling pathway in the neurodegeneration of microglia. Literature sources were searched using the key words “Alzheimer’s disease”, “microglia”, “dementia”, etc. The study was conducted based on an interactive group approach using a comprehensive literature review in the Web of Science, Scopus, Pubmed, Elsevier, and Springer databases. As a result of the analysis, it was found that one of the key participants in the process of neuroinflammation is microglia, which plays an important role in phagocytosis, transmission of neuronal signals and local immune response. The TREM2 gene, which normally promotes the phagocytosis of β-amyloid protein, was found to be a significant factor associated with dementia. Due to its effect on galectin-3, it causes the activation of microglia, which is of key importance in the development of neurodegenerative diseases. Another important factor turned out to be the mTOR signaling pathway, which is considered a key regulator of the main cellular and metabolic processes in microglia, however, the data of practical works on this pathway remain controversial. Thus, the study confirms the importance of the TREM2 gene and the mTOR signaling pathway in the development of Alzheimer's disease, which is related to their effects on microglia. The obtained results can be used for further research and development of strategies for the treatment of Alzheimer's disease.