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

Autor: Herrero-Lorenzo M; Department of Biomedicine, Faculty of Medicine, Institute of Neurosciences, University of Barcelona, Barcelona, Catalunya, Spain., Pérez-Pérez J; Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Catalunya, Spain.; Biomedical Research Institute (IIB-Sant Pau), Barcelona, Catalunya, Spain.; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Escaramís G; Department of Biomedicine, Faculty of Medicine, Institute of Neurosciences, University of Barcelona, Barcelona, Catalunya, Spain.; Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Spanish Ministry of Science and Innovation, Madrid, Spain., Martínez-Horta S; Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Catalunya, Spain.; Biomedical Research Institute (IIB-Sant Pau), Barcelona, Catalunya, Spain.; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Pérez-González R; Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Catalunya, Spain.; Biomedical Research Institute (IIB-Sant Pau), Barcelona, Catalunya, Spain.; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.; Alicante Institute for Health and Biomedical Research (ISABIAL) and Neuroscience Institute, Alicante, Spain., Rivas-Asensio E; Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Catalunya, Spain.; Biomedical Research Institute (IIB-Sant Pau), Barcelona, Catalunya, Spain.; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Kulisevsky J; Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Catalunya, Spain.; Biomedical Research Institute (IIB-Sant Pau), Barcelona, Catalunya, Spain.; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Gámez-Valero A; Department of Biomedicine, Faculty of Medicine, Institute of Neurosciences, University of Barcelona, Barcelona, Catalunya, Spain.; Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Spanish Ministry of Science and Innovation, Madrid, Spain., Martí E; Department of Biomedicine, Faculty of Medicine, Institute of Neurosciences, University of Barcelona, Barcelona, Catalunya, Spain.; Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Spanish Ministry of Science and Innovation, Madrid, Spain.; August Pi i Sunyer Biomedical research Institute (IDIBAPS), Barcelona, Catalunya, Spain.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2024 Oct; Vol. 13 (10), pp. e12522.
DOI: 10.1002/jev2.12522
Abstrakt: 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.
(© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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