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. 2014 Jul-Sep;28(3):226-33.
doi: 10.1097/WAD.0000000000000022.

Distinctive RNA expression profiles in blood associated with Alzheimer disease after accounting for white matter hyperintensities

Zhouxian Bai  1 , Boryana Stamova, Huichun Xu, Bradley P Ander, Jiajia Wang, Glen C Jickling, Xinhua Zhan, DaZhi Liu, Guangchun Han, Lee-Way Jin, Charles DeCarli, Hongxing Lei, Frank R Sharp
Affiliations

Distinctive RNA expression profiles in blood associated with Alzheimer disease after accounting for white matter hyperintensities

Zhouxian Bai et al. Alzheimer Dis Assoc Disord. 2014 Jul-Sep.

Abstract

Background: Defining the RNA transcriptome in Alzheimer Disease (AD) will help understand the disease mechanisms and provide biomarkers. Though the AD blood transcriptome has been studied, effects of white matter hyperintensities (WMH) were not considered. This study investigated the AD blood transcriptome and accounted for WMH.

Methods: RNA from whole blood was processed on whole-genome microarrays.

Results: A total of 293 probe sets were differentially expressed in AD versus controls, 5 of which were significant for WMH status. The 288 AD-specific probe sets classified subjects with 87.5% sensitivity and 90.5% specificity. They represented 188 genes of which 29 have been reported in prior AD blood and 89 in AD brain studies. Regulated blood genes included MMP9, MME (Neprilysin), TGFβ1, CA4, OCLN, ATM, TGM3, IGFR2, NOV, RNF213, BMX, LRRN1, CAMK2G, INSR, CTSD, SORCS1, SORL1, and TANC2.

Conclusions: RNA expression is altered in AD blood irrespective of WMH status. Some genes are shared with AD brain.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Principal Components Analysis (PCA) on the 288 probe sets that were differentially expressed between AD and control subjects (non-AD). AD subjects with WMH (AD, WMH – red dots) and AD without WMH (AD, non-WMH, pink dots) are included within the same centroids, and are separated from the centroids for control non-AD with WMH (non-AD, WMH – blue dots) and control non-AD without WMH (non-AD, non-WMH, light blue dots). The PCA accounts for 60% of the variance.
Figure 2
Figure 2
Cluster analysis for the 288 probe sets that separated AD from control (Non-AD). Note that subjects with WMH (WMH) and without WMH (Non-WMH) do not cluster separately. Subjects are on the Y axis, and genes/probe sets are on the X axis. Dark red represents a 2 fold increase in expression and dark green a 2 fold decrease in expression compared to controls.
Figure 3
Figure 3
Cellular functions for the 44 genes listed in Supplementary Table 1D. These genes represent those that were regulated in AD blood in this study (ANCOVA, p <0.005, |FC| > 1.2) and which were reported to be regulated in other AD blood studies, or were shown to be regulated in this study also using the rank product method and a |FC| threshold of > 1.5.
See this image and copyright information in PMC

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