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.

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Published in Acta Neuropathologica, v. 121, issue 2, p. 193-205.

© Springer-Verlag 2010

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The document available for download is the authors' post-peer-review final draft of the article.

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Funding Information

This study was supported by Grants R01 NS061933, R21AG036875, and P01 NS058484 from NIH.

Related Content

The online version of this article (doi:10.1007/s00401-010-0756-0) contains supplementary material, which is available to authorized users.

NIHMS264562-supplement-1.xls (2153 kB)
Supplemental Table 1. Complete microarray data. (XLS 2153 kb)

NIHMS264562-supplement-2.pdf (37 kB)
Supplemental Figure 1. Scatterplot shows the extremely high correlation in the results of miRNA profiling performed on the same sample, two months apart.

NIHMS264562-supplement-3.pdf (107 kB)
Supplemental Figure 2. Complete Northern blot data that were performed on 10 different miRNAs with relatively high expression according to the microarrays used in the current studies despite lack of previous evidence of brain expression.