Department of Pathology, Sanders-Brown Center on Aging, University of Kentucky Medical Center, University of Kentucky, Lexington, 40536-0230, USA.
Acta Neuropathol. 2011 Feb;121(2):193-205. doi: 10.1007/s00401-010-0756-0. Epub 2010 Oct 10.
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.
为了深入了解阿尔茨海默病（AD）病变范围内大脑灰质（GM）和白质（WM）之间 miRNA 谱的差异，我们评估了人类大脑皮质 GM 和 WM 中的 miRNA 表达。从额中颞上和中部大脑皮质的 GM 和 WM 部分（N = 10 名老年女性，死后间隔 < 4 小时）中分别分离 RNA。使用最先进的 Exiqon（©）LNA-microarray 进行 miRNA 分析实验。根据 microarray，有一部分 miRNA 似乎表达很强，但根据 Northern blot 分析，它们似乎不是常规 miRNA。一些特征明确的 miRNA 如预期那样在 WM 中大量富集。然而，与早期 AD 相关病理存在相关的 miRNA 表达变化大部分发生在 GM 中。我们证实 GM 中一组 miRNA 的下调（包括几个 miR-15/107 基因和 miR-29 同源物）与相邻组织中检测到的弥漫性淀粉样斑块密度密切相关。WM 中也有一些 miRNA 表达不同，包括在 AD 中下调的 miR-212 和在 AD 中上调的 miR-424。某些 miRNA 的表达与不同病例中的其他 miRNA 相关，并且特定 miRNA 子集与 AD 相关病理相关联地表达。这些数据支持这样的假设，即 GM 中的 miRNA 表达模式可能在 AD 的发病机制中起作用，因为在疾病早期观察到的 miRNA 表达的总体变化预计会导致基因表达的深刻变化。
