RT Journal Article SR Electronic T1 Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 485 OP 493 DO 10.1136/jnnp-2020-324647 VO 92 IS 5 A1 Virgilio Kmetzsch A1 Vincent Anquetil A1 Dario Saracino A1 Daisy Rinaldi A1 Agnès Camuzat A1 Thomas Gareau A1 Ludmila Jornea A1 Sylvie Forlani A1 Philippe Couratier A1 David Wallon A1 Florence Pasquier A1 Noémie Robil A1 Pierre de la Grange A1 Ivan Moszer A1 Isabelle Le Ber A1 Olivier Colliot A1 Emmanuelle Becker A1 , YR 2021 UL http://jnnp.bmj.com/content/92/5/485.abstract AB 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.Data are available upon reasonable request (isabelle.leber@upmc.fr).