microRNA‐based predictor for diagnosis of frontotemporal dementia

Author:

Magen Iddo12ORCID,Yacovzada Nancy‐Sarah12ORCID,Warren Jason D.3,Heller Carolin34ORCID,Swift Imogen34ORCID,Bobeva Yoana5,Malaspina Andrea56ORCID,Rohrer Jonathan D.3ORCID,Fratta Pietro6ORCID,Hornstein Eran12ORCID

Affiliation:

1. Department of Molecular Genetics Weizmann Institute of Science Rehovot Israel

2. Department of Molecular Neuroscience Weizmann Institute of Science Rehovot Israel

3. Dementia Research Centre Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology London UK

4. UK Dementia Research Institute, Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK

5. Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK

6. Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London UK

Abstract

AbstractAimsThis study aimed to explore the non‐linear relationships between cell‐free microRNAs (miRNAs) and their contribution to prediction of Frontotemporal dementia (FTD), an early onset dementia that is clinically heterogeneous, and too often suffers from delayed diagnosis.MethodsWe initially studied a training cohort of 219 subjects (135 FTD and 84 non‐neurodegenerative controls) and then validated the results in a cohort of 74 subjects (33 FTD and 41 controls).ResultsOn the basis of cell‐free plasma miRNA profiling by next generation sequencing and machine learning approaches, we develop a non‐linear prediction model that accurately distinguishes FTD from non‐neurodegenerative controls in ~90% of cases.ConclusionsThe fascinating potential of diagnostic miRNA biomarkers might enable early‐stage detection and a cost‐effective screening approach for clinical trials that can facilitate drug development.

Funder

ALS Association

Alzheimer's Research Foundation

Fondation Thierry Latran

FP7 Ideas: European Research Council

French Muscular Dystrophy Association

Israel Science Foundation

Minerva Foundation

Motor Neurone Disease Association

Target ALS

Teva Pharmaceutical Industries

Wolfson Foundation

Alzheimer's Society

UCLH Biomedical Research Centre

Publisher

Wiley

Subject

Physiology (medical),Neurology (clinical),Neurology,Histology,Pathology and Forensic Medicine

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