TY - JOUR T1 - Plasma microRNA signature in presymptomatic and symptomatic subjects with <em>C9orf72</em>-associated frontotemporal dementia and amyotrophic lateral sclerosis JF - Journal of Neurology, Neurosurgery &amp; Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 485 LP - 493 DO - 10.1136/jnnp-2020-324647 VL - 92 IS - 5 AU - Virgilio Kmetzsch AU - Vincent Anquetil AU - Dario Saracino AU - Daisy Rinaldi AU - Agnès Camuzat AU - Thomas Gareau AU - Ludmila Jornea AU - Sylvie Forlani AU - Philippe Couratier AU - David Wallon AU - Florence Pasquier AU - Noémie Robil AU - Pierre de la Grange AU - Ivan Moszer AU - Isabelle Le Ber AU - Olivier Colliot AU - Emmanuelle Becker A2 - , Y1 - 2021/05/01 UR - http://jnnp.bmj.com/content/92/5/485.abstract N2 - 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). ER -