Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington's disease
Herrero-Lorenzo, Marina (Universitat de Barcelona)
Pérez-Pérez, Jesús (Institut de Recerca Sant Pau)
Escaramís, G. (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Martínez-Horta, Saul (Institut de Recerca Sant Pau)
Pérez-González, R. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Rivas-Asensio, E. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Kulisevsky, Jaime (Institut de Recerca Sant Pau)
Gámez-Valero, A. (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Martí, E. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Universitat Autònoma de Barcelona

Date:	2024
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.
Grants:	Agencia Estatal de Investigación PID2020-113953RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Huntington's disease ; Biomarker ; Extracellular vesicles ; Mirna ; Premanifest ; Small RNA ; Trf
Published in:	Journal of extracellular vesicles, Vol. 13 Núm. 10 (october 2024) , p. e12522, ISSN 2001-3078

DOI: 10.1002/jev2.12522
PMID: 39377487

21 p, 2.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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