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MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid
Mareike Müller1, H Bea Kuiperij, Jurgen A Claassen
1Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Centre, Nijmegen, the Netherlands.
Abstract:
MicroRNAs (miRNAs) are small, noncoding RNAs that function in complex networks to regulate protein expression. In the brain, they are involved in development and synaptic plasticity. In this study, we aimed to identify miRNAs with a differential expression in either hippocampus or cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and age-matched nondemented control subjects using quantitative polymerase chain reaction. In hippocampus, we also differentiated between AD patients with an intermediate stage, according to Braak III/IV stage, and a late stage, characterized according to Braak VI stage. Eight selected miRNAs were analyzed in hippocampus, and the expression of miR-16, miR-34c, miR-107, miR-128a, and miR-146a were differentially regulated. In CSF, out of 8 selected miRNAs only miR-16 and miR-146a could be reliably detected. In addition, we identified an effect of blood contamination on the CSF levels of miR-16, miR-24, and miR-146a. For group comparisons, we therefore selected CSF samples absent of, or containing only low numbers of blood cells. Levels of miR-146a were significantly decreased in CSF of AD patients. In conclusion, the abnormal expression of several miRNAs in hippocampus of intermediate- and late-stage AD patients suggests their involvement in AD pathogenesis, and low levels of miR-146a in CSF were associated with AD.
Insights
Alzheimer's disease (AD) is linked to altered microRNA (miRNA) expression in the brain. Specifically, lower levels of miR-146a in cerebrospinal fluid (CSF) were observed in AD patients, suggesting its role in the disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of protein expression, crucial for brain development and function.
- Dysregulation of miRNAs is implicated in neurodegenerative diseases like Alzheimer's disease (AD).
Purpose of the Study:
- To identify differentially expressed miRNAs in the hippocampus and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients.
- To investigate the correlation between miRNA expression levels and AD staging.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) was used to analyze miRNA expression in hippocampus and CSF samples.
- AD patients were categorized into intermediate (Braak III/IV) and late (Braak VI) stages.
- CSF samples were carefully selected to minimize blood contamination effects.
Main Results:
- Several miRNAs, including miR-16, miR-34c, miR-107, miR-128a, and miR-146a, showed differential expression in the hippocampus of AD patients.
- Only miR-16 and miR-146a were reliably detected in CSF.
- Significantly decreased levels of miR-146a were found in the CSF of AD patients.
- Blood contamination was identified as a confounding factor for CSF miRNA levels.
Conclusions:
- Aberrant miRNA expression in the hippocampus suggests their involvement in the pathogenesis of intermediate and late-stage AD.
- Reduced miR-146a levels in CSF are associated with Alzheimer's disease.
