Validation of microRNAs in Cerebrospinal Fluid as Biomarkers for Different Forms of Dementia in a Multicenter Study

Article type: Research Article

Authors: Müller, Mareike^{a; b} | Kuiperij, H. Bea^{a; b} | Versleijen, Alexandra A.M.^b | Chiasserini, Davide^c | Farotti, Lucia^c | Baschieri, Francesca^c | Parnetti, Lucilla^c | Struyfs, Hanne^d | De Roeck, Naomi^d | Luyckx, Jill^d | Engelborghs, Sebastiaan^{d; e} | Claassen, Jurgen A.^f | Verbeek, Marcel M.^{a; b; *}

Affiliations: [a] Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands | [b] Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands | [c] Department of Medicine, Laboratory of Clinical Neurochemistry, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy | [d] Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [e] Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium | [f] Department of Geriatric Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: Dr. Marcel M. Verbeek, Department of Neurology, 830 TML, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 243615192; Fax: +31 2436 68754; E-mail: Marcel.Verbeek@radboudumc.nl.; http://www.neurochemistry.nl.

Abstract: MicroRNAs (miRNAs) regulate translational inhibition of proteins, but are also detected in body fluids, including cerebrospinal fluid (CSF), where they may serve as disease-specific biomarkers. Previously, we showed differential expression of miR-146a, miR-29a, and miR-125b in the CSF of Alzheimer’s disease (AD) patients versus controls. In this study, we aim to confirm these findings by using larger, independent sample cohorts of AD patients and controls from three different centers. Furthermore, we aim to identify confounding factors that possibly arise using such a multicenter approach. The study was extended by including patients diagnosed with mild cognitive impairment due to AD, frontotemporal dementia and dementia with Lewy bodies. Previous results of decreased miR-146a levels in AD patients compared to controls were confirmed in one center. When samples from all three centers were combined, several confounding factors were identified. After controlling for these factors, we did not identify differences in miRNA levels between the different groups. However, we provide suggestions to circumvent various pitfalls when measuring miRNAs in CSF to improve future studies.

Keywords: Alzheimer’s disease, cerebrospinal fluid, frontotemporal dementia, Lewy body disease, microRNAs, mild cognitive impairment

DOI: 10.3233/JAD-160038

Journal: Journal of Alzheimer's Disease, vol. 52, no. 4, pp. 1321-1333, 2016