microRNAS no líquido cefalorraquidiano associados à doença de Alzheimer: uma revisão sistemática e análise de vias usando a abordagem de aprendizado de máquina.

Abstract

The increase in life expectancy and the aging population have contributed to the growth in the prevalence of Alzheimer's disease (AD), as aging is one of the risk factors for the development of the sporadic form of the disease. The diagnosis of AD is primarily based on clinical evaluation and requires the expertise of highly trained professionals for a conclusive diagnosis. However, due to the complexity of the disease and the need for more precise methods, research on biomarkers has gained increasing importance. In recent times, there has been a significant increase in interest in the role of microRNAs (miRNAs) in gene expression regulation and their association with AD. MiRNAs are small non-coding RNA molecules that play a crucial role in regulating cellular processes. Several miRNAs have been identified as potential markers for the diagnosis and progression of AD. This study aimed to search for differentially expressed miRNAs in the cerebrospinal fluid (CSF) of AD patients compared to cognitively healthy individuals using public databases and machine learning tools, with the validation of the results in a systematic review and the proposal of regulated biological pathways. To do this, the initial search was conducted on the GEO Database platform, and the LightGBM algorithm was applied. Subsequently, the systematic review was performed using the PECO framework – Population (P): elderly individuals, Exposure (E): Alzheimer's disease, Control (C): cognitively healthy individuals, Outcome (O): differentially expressed miRNAs in CSF, utilizing the electronic repositories: MEDLINE/PubMed, Scopus, Cinahl, Web of Science, and Embase. Pathway analysis was conducted using miRTarBase. After overlapping the results obtained by the algorithm and the systematic review, seven miRNAs were identified as the most differentially expressed in the CSF of individuals with AD: miRNA-1274a, miRNA-193a-5p, miRNA-28-3p, miRNA-30a-3p, miRNA-145, miRNA-19b, and miRNA-143. In the pathway enrichment analysis, the following pathways were identified: DNA damage response by ATM, ERBB signaling, intracellular second messenger signaling, MAPK signaling, and TGF-beta signaling, all of which have a role in the pathophysiology of AD. The results suggest that miRNA-1274a, miRNA-193a-5p, miRNA-28-3p, miRNA-30a-3p, miRNA-145, miRNA-19b, and miRNA-143 may be involved in the molecular mechanisms and biological pathways associated with the disease and could potentially serve as therapeutic targets for AD in the future.