MicroRNA (
miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM
miRNA repertoires across a range of
Alzheimer's disease (AD) pathology.
RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval < 4 h).
miRNA profiling experiments were performed using state-of-the-art Exiqon(©) LNA-microarrays. A subset of
miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional
miRNAs according to Northern blot analyses. Some well-characterized
miRNAs were substantially enriched in WM as expected. However, most of the
miRNA expression variability that correlated with the presence of early AD-related pathology was seen in GM. We confirm that downregulation of a set of
miRNAs in GM (including several miR-15/107 genes and miR-29 paralogs) correlated strongly with the density of diffuse
amyloid plaques detected in adjacent tissue. A few
miRNAs were differentially expressed in WM, including miR-212 that is downregulated in AD and miR-424 which is upregulated in AD. The expression of certain
miRNAs correlates with other
miRNAs across different cases, and particular subsets of
miRNAs are coordinately expressed in relation to AD-related pathology. These data support the hypothesis that patterns of
miRNA expression in cortical GM may contribute to AD pathogenetically, because the aggregate change in
miRNA expression observed early in the disease would be predicted to cause profound changes in gene expression.