Characterization of tRNA-derived fragments in the small neuron-derived extracellular vesicles of Alzheimer's disease patients

Arioz B. I., Binokay L., Tastan B., Genc B., Cotuk A., DURSUN E., ...More

Brain Research, vol.1862, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1862
  • Publication Date: 2025
  • Doi Number: 10.1016/j.brainres.2025.149730
  • Journal Name: Brain Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Linguistics & Language Behavior Abstracts, Psycinfo, Veterinary Science Database
  • Keywords: Alzheimer's disease, Biomarker, non-coding RNAs, tRNA-derived fragments
  • Istanbul University Affiliated: Yes

Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. The development of neurofibrillary tangles and amyloid plaques are pathological hallmarks of the disease. Molecular mechanisms underlying AD are multifaceted, extracellular vesicles contribute disease pathogenesis via cargo molecules such as DNA, protein, RNA and non-coding RNAs. tRNA-derived fragments (tRFs) are small non-coding RNAs with regulatory functions and their alterations have been demonstrated in various diseases. In this study, we aimed to investigate peripherally altered tRFs in small neuron-derived extracellular vesicles (sNDEVs) from AD patients. Method: 83 AD patients and 39 healthy controls were enrolled to study. After total sEVs isolation with ultracentrifugation, sNDEVs were enriched with CD171. EVs were characterized using Western blot, nanoparticle tracking analysis (NTA), and STEM. We utilized next-generation sequencing to analyze the expression profiles of tRFs in sNDEVs from AD patients compared to healthy controls. For the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we employed the ShinyGO web tool. The alterations of two differentially expressed tRNA fragments in the sNDEVs of AD patients, were confirmed using the RT-qPCR method. Result: In our study we found that three tRFs were significantly upregulated, and 10 tRFs were significantly downregulated. Then, we confirmed the upregulation of tRF-20-1HPSR9O9 and the downregulation of tRF-33-RM7KYUPRENRHD2 on a larger population with the RT-qPCR method. In the KEGG and GO analyses using targets of detected tRFs, we found significant terms related to brain and neurons, such as neuron projection morphogenesis, neuron differentiation, long-term depression and glutamatergic synapse. Conclusion: Our study suggests that tRFs in sNDEVs of AD patients differ from controls and the role of these tRFs in disease pathogenesis be investigated in further studies.