MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid

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.