Validation of microRNAs in Cerebrospinal Fluid as Biomarkers for Different Forms of Dementia in a Multicenter Study.
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.
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Mareike
M
Müller
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
H Bea
HB
Kuiperij
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Alexandra A M
AA
Versleijen
Department of Medicine, Laboratory of Clinical Neurochemistry, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
Davide
D
Chiasserini
Department of Medicine, Laboratory of Clinical Neurochemistry, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
Lucia
L
Farotti
Department of Medicine, Laboratory of Clinical Neurochemistry, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
Francesca
F
Baschieri
Department of Medicine, Laboratory of Clinical Neurochemistry, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
Lucilla
L
Parnetti
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Hanne
H
Struyfs
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Naomi
N
De Roeck
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Jill
J
Luyckx
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
Sebastiaan
S
Engelborghs
Department of Geriatric Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
Jurgen A
JA
Claassen
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Marcel M
MM
Verbeek
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid*; D008875:Middle Aged
D015415:Biomarkers; C531888:MIRN125 microRNA, human; C542542:MIRN146 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs
Alzheimer’s disease; Lewy body disease; cerebrospinal fluid; frontotemporal dementia; microRNAs; mild cognitive impairment