Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia

Article type: Research Article

Authors: Piscopo, Paola^a | Grasso, Margherita^b | Puopolo, Maria^a | D’Acunto, Emanuela^{a; c} | Talarico, Giuseppina^d | Crestini, Alessio^a | Gasparini, Marina^d | Campopiano, Rosa^e | Gambardella, Stefano^e | Castellano, Anna Elisa^e | Bruno, Giuseppe^d | Denti, Michela A.^{b; 1; *} | Confaloni, Annamaria^{a; 1; *}

Affiliations: [a] Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy | [b] Centre for Integrative Biology, University of Trento, Trento, Italy | [c] Department of Biology and Biotechnologies ‘Charles Darwin’, University of Rome “Sapienza”, Rome, Italy | [d] Department of Human Neuroscience, University of Rome “Sapienza”, Rome, Italy | [e] Department of Neurology, IRCCS Neuromed Institute, Pozzilli, IS, Italy

Correspondence: [*] Correspondence to: Annamaria Confaloni, Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Tel.: +39 0649902930; Fax: +39 49902040; E-mail: [email protected] and Michela A. Denti, Laboratory of RNA Biology and Biotechnology, Centre for Integrative Biology - University of Trento, Via Sommarive 9, 38123 Trento, Italy. Tel.: +39 0461283820; Fax: +39 0461283937; E-mail: WEML [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Given the heterogeneous nature of frontotemporal dementia (FTD), sensitive biomarkers are greatly needed for the accurate diagnosis of this neurodegenerative disorder. Circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system, especially in aging. The objective of the study was to evaluate if some circulating miRNAs linked with apoptosis (miR-29b-3p, miR-34a-5p, miR-16-5p, miR-17-5p, miR-107, miR-19b-3p, let-7b-5p, miR-26b-5p, and 127-3p) were able to distinguish between FTD patients and healthy controls. For this study, we enrolled 127 subjects, including 54 patients with FTD, 20 patients with Alzheimer’s disease (AD), and 53 healthy controls. The qRT-PCR analysis showed a downregulation of miR-127-3p in FTD compared to controls, while the levels of other miRNAs remained unchanged. Then, miR-127-3p expression was also analyzed in AD patients, finding a different expression between two patient groups. A receiver operating characteristic curve was then created for miR-127-3p to discriminate FTD versus AD (AUC: 0.8986), and versus healthy controls (AUC: 0.8057). In conclusion, miR-127-3p could help to diagnose FTD and to distinguish it from AD.

Keywords: Biomarker, differential diagnosis, frontotemporal dementia, miR-127-3p, miRNA

DOI: 10.3233/JAD-180364

Journal: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 455-464, 2018