Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington's disease

Autor: Marina Herrero‐Lorenzo, Jesús Pérez‐Pérez, Georgia Escaramís, Saül Martínez‐Horta, Rocío Pérez‐González, Elisa Rivas‐Asensio, Jaime Kulisevsky, Ana Gámez‐Valero, Eulàlia Martí
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 13, Iss 10, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2001-3078
43036945
DOI: 10.1002/jev2.12522
Popis: Abstract Despite the advances in the understanding of Huntington's disease (HD), there is a need for molecular biomarkers to categorize mutation carriers during the preclinical stage of the disease preceding functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological processes. Here, using an optimized method for plasma extracellular vesicles (EVs) purification and an exhaustive analysis pipeline of sRNA sequencing data, we show that EV‐sRNAs are downregulated early in mutation carriers and that this deregulation is associated with premanifest cognitive performance. Seven candidate sRNAs (tRF‐Glu‐CTC, tRF‐Gly‐GCC, miR‐451a, miR‐21‐5p, miR‐26a‐5p, miR‐27a‐3p and let7a‐5p) were validated in additional subjects, showing a significant diagnostic accuracy at premanifest stages. Of these, miR‐21‐5p was significantly decreased over time in a longitudinal study; and miR‐21‐5p and miR‐26a‐5p levels correlated with cognitive changes in the premanifest cohort. In summary, the present results suggest that deregulated plasma EV‐sRNAs define an early biosignature in mutation carriers with specific species highlighting the progression and cognitive changes occurring at the premanifest stage.
Databáze: Directory of Open Access Journals
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