Title :

Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author(s) :

Kmetzsch, V. [Auteur]
Centre Inria de Sorbonne Université
Anquetil, V. [Auteur]
Centre Inria de Sorbonne Université
Saracino, D. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Centre Inria de Sorbonne Université
Rinaldi, D. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Institut du Cerveau = Paris Brain Institute [ICM]
Camuzat, A. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Gareau, T. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Jornea, L. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Forlani, S. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Couratier, P. [Auteur]
Service de Neurologie [CHU Limoges]
Wallon, D. [Auteur]
Service de neurologie [Rouen]
Pasquier, Florence [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Robil, N. [Auteur]
GenoSplice [Paris]
De La Grange, P. [Auteur]
GenoSplice [Paris]
Moszer, I. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Le Ber, I. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Institut du Cerveau = Paris Brain Institute [ICM]
Colliot, O. [Auteur]
Institut du Cerveau = Paris Brain Institute [ICM]
Becker, Emmanuelle [Auteur]
Institut de Recherche en Informatique et Systèmes Aléatoires [IRISA]

Journal title :

Journal of Neurology, Neurosurgery and Psychiatry

Volume number :

92

Pages :

485–493

Publisher :

BMJ Journals

Publication date :

2020-11-29

ISSN :

1468-330X

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-16T02:24:02Z
2024-11-13T08:11:00Z
2024-11-13T09:31:31Z