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Background <p>Frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders that lead to progressive changes in language, behavior, personality, and movement. Accounting for approximately 60% of cases, the behavioral variant (bvFTD) represents the most common clinical presentation of FTD. MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation and are expressed in various biological fluids. Considering bvFTD as an inflammatory disorder, this study investigated the expression of inflammation-related miRNAs in individuals with bvFTD compared with age- and sex-matched cognitively healthy controls.</p> Methods <p>Twenty patients with bvFTD and 20 cognitively healthy controls, matched for age and sex, were included in the study. Serum levels of miRNA-30c-5p and miRNA-125a-5p were analyzed.</p> Results <p>miRNA-125a-5p expression was upregulated in individuals with bvFTD compared with controls (fold change = 2.02). No significant differences between groups were observed for miRNA-30c-5p. An inverse correlation was identified between miRNA-125a-5p expression and age within the bvFTD group. Pathway enrichment analysis revealed that miRNA-125a-5p was significantly involved in the regulation of genes associated with insulin receptor signaling, SUMOylation, SUMO E3 ligase–mediated protein modification, SUMOylation of chromatin organization proteins, estrogen-dependent gene expression, extracellular exosome pathways, neuron migration, microtubule dynamics, and nervous system development.</p> Conclusions <p>These findings suggest that miRNA-125a-5p may play an important role in FTD-related biological pathways, underscoring its potential as a molecular marker in the pathophysiology of this disorder.</p>

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Biological pathways related to mirna-125a-5p in behavioral variant of frontotemporal dementia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Jessica Diniz Pereira,
  • Leticia Moreira Silva,
  • Mhai Ozawa,
  • Jéssica Abdo Gonçalves Tosatti,
  • Stephanny Pinto Oliveira Lima,
  • Isabela Resende Silva,
  • Vinicius Ribeiro Jeunon,
  • Maria das Graças Carvalho,
  • Elisa de Paula França Resende,
  • Leonardo Cruz de Souza,
  • Paulo Caramelli,
  • Karina Braga Gomes

摘要

Background

Frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders that lead to progressive changes in language, behavior, personality, and movement. Accounting for approximately 60% of cases, the behavioral variant (bvFTD) represents the most common clinical presentation of FTD. MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation and are expressed in various biological fluids. Considering bvFTD as an inflammatory disorder, this study investigated the expression of inflammation-related miRNAs in individuals with bvFTD compared with age- and sex-matched cognitively healthy controls.

Methods

Twenty patients with bvFTD and 20 cognitively healthy controls, matched for age and sex, were included in the study. Serum levels of miRNA-30c-5p and miRNA-125a-5p were analyzed.

Results

miRNA-125a-5p expression was upregulated in individuals with bvFTD compared with controls (fold change = 2.02). No significant differences between groups were observed for miRNA-30c-5p. An inverse correlation was identified between miRNA-125a-5p expression and age within the bvFTD group. Pathway enrichment analysis revealed that miRNA-125a-5p was significantly involved in the regulation of genes associated with insulin receptor signaling, SUMOylation, SUMO E3 ligase–mediated protein modification, SUMOylation of chromatin organization proteins, estrogen-dependent gene expression, extracellular exosome pathways, neuron migration, microtubule dynamics, and nervous system development.

Conclusions

These findings suggest that miRNA-125a-5p may play an important role in FTD-related biological pathways, underscoring its potential as a molecular marker in the pathophysiology of this disorder.