O papel dos receptores da família TREM no envelhecimento: análise bibliométrica e protocolo de revisão sistemática sobre sTREM-1 e sTREM-2 na doença de Alzheimer

Abstract

Introduction: Aging is a complex physiological process that involves physiological changes and increases susceptibility to disease. In this phenomenon, one of the biological systems most affected by these changes is the immune system. This process is known as immunosenescence and is interrelated with the state of low-grade chronic inflammation that occurs during aging. Therefore, studies aimed at expanding specific knowledge in this context by investigating molecules directly involved in inflammation, such as the Triggering Receptor Expressed on Myeloid Cells (TREM) family receptors, are of great importance. Members of this family, particularly TREM-1 and TREM-2, have been described as playing a central role in the development and control of inflammation, respectively. Objectives: To analyze the scientific literature on TREM-1 and TREM-2 in the context of aging, identifying the structure of knowledge, key themes, and trends in the field, as well as to investigate changes in the soluble forms of these receptors in older adults diagnosed with Alzheimer’s disease (AD), a condition commonly associated with aging. Methods: For the bibliometric review, publication metadata from Web of Science were analyzed using the bibliometrix package in R and its graphical interface, Biblioshiny, as well as VOSViewer. Analyses were conducted on performance indicators and science mapping. Regarding the systematic review, it follows the guidelines proposed by the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) 2020, and its research question was formulated based on the results from the bibliometric analysis. The research question informed the components of the search strategy for PubMed, Embase, and Web of Science databases, as well as the eligibility criteria. To conduct the review, the following steps will be performed: study selection, data extraction, assessment of risk of bias, data synthesis, and assessment of certainty of evidence. Results: The bibliometric analysis included 606 articles published in 314 journals between 2004 and November 2025. The data showed an annual growth rate of 22.67% in publications, an average document age of 5.46 years, and an average of 37.1 citations per document. The results also indicate that the research field is dominated by high-income countries, with the United States leading scientific production, and that there is a thematic predominance regarding the role of TREM-2 in neurodegeneration. Conclusions: The bibliometric analysis suggests that this field appears to focus on the involvement of TREM-1 and TREM-2 in neurodegenerative diseases—particularly the role of TREM-2 in AD—rather than their role in physiological aging itself. Relevance and impact: This study provides a clearer visualization of the knowledge structure and thematic trends in scientific production in this research field and highlights the need for further primary studies on the relationship among TREM-1, TREM2, and physiological aging. In addition, the bibliometric results were used to design the systematic review, which can be used to inform health decisions related to older adults.