MicroRNA signatures in genetic frontotemporal dementia and amyotrophic lateral sclerosis

• Published in: Annals of clinical and translational neurology Vol. 9; no. 11; pp. 1778 - 1791
• Main Authors: Kmetzsch, Virgilio, Latouche, Morwena, Saracino, Dario, Rinaldi, Daisy, Camuzat, Agnès, Gareau, Thomas, Le Ber, Isabelle, Colliot, Olivier, Becker, Emmanuelle
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.11.2022; Wiley; John Wiley and Sons Inc
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Bioengineering; Biomarkers; C9orf72 Protein - genetics; Computer Science; Computer Vision and Pattern Recognition; Dementia; Engineering Sciences; Frontotemporal Dementia - genetics; Frontotemporal Dementia - metabolism; Humans; Image Processing; Imaging; Life Sciences; Medical Imaging; MicroRNAs; MicroRNAs - genetics; Mutation; Neurobiology; Neurons and Cognition; Pick Disease of the Brain; Signal and Image processing
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51674

Objective MicroRNAs are promising biomarkers of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but discrepant results between studies have so far hampered their use in clinical trials. We aim to assess all previously identified circulating microRNA signatures as potential biomarkers of genetic FTD and/or ALS, using homogeneous, independent validation cohorts of C9orf72 and GRN mutation carriers. Methods 104 individuals carrying a C9orf72 or a GRN mutation, along with 31 controls, were recruited through the French research network on FTD/ALS. All subjects underwent blood sampling, from which circulating microRNAs were extracted. We measured differences in the expression levels of 65 microRNAs, selected from 15 published studies about FTD or ALS, between 31 controls, 17 C9orf72 presymptomatic subjects, and 29 C9orf72 patients. We also assessed differences in the expression levels of 30 microRNAs, selected from five studies about FTD, between 31 controls, 30 GRN presymptomatic subjects, and 28 GRN patients. Results More than half (35/65) of the selected microRNAs were differentially expressed in the C9orf72 cohort, while only a small proportion (5/30) of microRNAs were differentially expressed in the GRN cohort. In multivariate analyses, only individuals in the C9orf72 cohort could be adequately classified (ROC AUC up to 0.98 for controls versus presymptomatic subjects, 0.94 for controls versus patients, and 0.77 for presymptomatic subjects versus patients) with some of the signatures. Interpretation Our results suggest that previously identified microRNAs using sporadic or mixed cohorts of FTD and ALS patients could potentially serve as biomarkers of C9orf72‐associated disease, but not GRN‐associated disease.