Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. Issue 5 (25th November 2020)

• Record Type: Journal Article
• Authors: Kmetzsch, Virgilio; Anquetil, Vincent; Saracino, Dario; Rinaldi, Daisy; Camuzat, Agnès; Gareau, Thomas; Jornea, Ludmila; Forlani, Sylvie; Couratier, Philippe; Wallon, David; Pasquier, Florence; Robil, Noémie; de la Grange, Pierre; Moszer, Ivan; Le Ber, Isabelle; Colliot, Olivier; Becker, Emmanuelle
• Other Names: author non-byline.; Benchetrit Eve author non-byline.; Bertrand Anne author non-byline.; Bissery Anne author non-byline.; Boncoeur Marie-Paule author non-byline.; Bombois Stéphanie author non-byline.; Camuzat Agnès author non-byline.; Chastan Mathieu author non-byline.; Chen Yaohua author non-byline.; Chupin Marie author non-byline.; Colliot Olivier author non-byline.; Couratier Philippe author non-byline.; Delbeuck Xavier author non-byline.; Deramecourt Vincent author non-byline.; Delmaire Christine author non-byline.; Gerardin Emmanuel author non-byline.; Hossein-Foucher Claude author non-byline.; Dubois Bruno author non-byline.; Habert Marie-Odile author non-byline.; Hannequin Didier author non-byline.; Lautrete Géraldine author non-byline.; Lebouvier Thibaud author non-byline.; Ber Isabelle Le author non-byline.; Toullec Benjamin Le author non-byline.; Levy Richard author non-byline.; Martinaud Olivier author non-byline.; Martineau Kelly author non-byline.; Mackowiak Marie-Anne author non-byline.; Monteil Jacques author non-byline.; Pasquier Florence author non-byline.; Petyt Gregory author non-byline.; Pradat Pierre-François author non-byline.; Oya Assi-Hervé author non-byline.; Rametti-Lacroux Armelle author non-byline.; Rinaldi Daisy author non-byline.; Rollin-Sillaire Adeline author non-byline.; Salachas François author non-byline.; Sayah Sabrina author non-byline.; Wallon David author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 92:Issue 5(2021)
• Page Start: 485
• Page End: 493
• Publication Date: 2020-11-25
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2020-324647
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Objective: To identify potential biomarkers of preclinical and clinical progression in chromosome 9 open reading frame 72 gene ( C9orf72) -associated disease by assessing the expression levels of plasma microRNAs (miRNAs) in C9orf72 patients and presymptomatic carriers. Methods: The PREV-DEMALS study is a prospective study including 22 C9orf72 patients, 45 presymptomatic C9orf72 mutation carriers and 43 controls. We assessed the expression levels of 2576 miRNAs, among which 589 were above noise level, in plasma samples of all participants using RNA sequencing. The expression levels of the differentially expressed miRNAs between patients, presymptomatic carriers and controls were further used to build logistic regression classifiers. Results: Four miRNAs were differentially expressed between patients and controls: miR-34a-5p and miR-345-5p were overexpressed, while miR-200c-3p and miR-10a-3p were underexpressed in patients. MiR-34a-5p was also overexpressed in presymptomatic carriers compared with healthy controls, suggesting that miR-34a-5p expression is deregulated in cases with C9orf72 mutation. Moreover, miR-345-5p was also overexpressed in patients compared with presymptomatic carriers, which supports the correlation of miR-345-5p expression with the progression of C9orf72 -associated disease. Together, miR-200c-3p and miR-10a-3p underexpression might be associated with full-blown disease. Four presymptomatic subjects in transitional/prodromal stage, close to the disease conversion, exhibited a stronger similarity with the expression levels of patients. Conclusions: We identified a signature of four miRNAs differentially expressed in plasma between clinical conditions that have potential to represent progression biomarkers for C9orf72 -associated frontotemporal dementia and amyotrophic lateral sclerosis. This study suggests that dysregulation of miRNAs is dynamically altered throughout neurodegenerative diseases progression, and can be detectable even long before clinical onset. Trial registration number: NCT02590276 .