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Published on: July 23, 2012
Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain
Huichun Xu1, Boryana Stamova, Glen Jickling
1Department of Neurology and M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA. huixu@ucdavis.edu
Background And Purpose:
White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain.
Methods:
Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH-), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance.
Results:
Two hundred forty-one genes were differentially regulated at ± 1.2-fold difference (P < 0.005) in subjects with WMH+ as compared to WMH-, regardless of cognitive status and 50 genes were differentially regulated with ± 1.5-fold difference (P < 0.005). Cluster and principal components analyses showed that the expression profiles for these genes distinguished WMH+ from WMH- subjects. Function analyses suggested that WMH-specific genes were associated with oxidative stress, inflammation, detoxification, and hormone signaling, and included genes associated with oligodendrocyte proliferation, axon repair, long-term potentiation, and neurotransmission.
Conclusions:
The unique RNA expression profile in blood associated with WMH is consistent with roles of systemic oxidative stress and inflammation, as well as other potential processes in the pathogenesis or consequences of WMH.
Insights
Blood RNA expression reveals distinct profiles in individuals with white matter hyperintensities (WMH), suggesting systemic oxidative stress and inflammation play roles in WMH pathogenesis.
Area of Science:
- Neuroscience
- Genomics
- Biomarkers
Background:
- White matter hyperintensities (WMH) are MRI-detected brain lesions linked to aging and cognitive decline.
- The underlying causes of WMH remain incompletely understood.
- Investigating systemic markers may offer insights into WMH pathogenesis.
Purpose of the Study:
- To analyze blood RNA expression in individuals with and without extensive WMH.
- To identify potential molecular mechanisms contributing to WMH.
- To explore links between systemic processes and WMH development.
Main Methods:
- Blood RNA was extracted from 20 individuals with extensive WMH (WMH+) and 18 with minimal WMH (WMH-).
- Whole genome gene expression profiling was performed using Affymetrix microarrays.
- Differential gene expression was analyzed using covariance, with cluster and principal component analyses.
Main Results:
- 241 genes showed differential regulation (±1.2-fold, P < 0.005) between WMH+ and WMH- groups.
- 50 genes exhibited greater differential regulation (±1.5-fold, P < 0.005).
- Expression profiles clearly distinguished WMH+ from WMH- subjects, implicating oxidative stress, inflammation, and hormone signaling.
Conclusions:
- A unique blood RNA expression signature is associated with WMH.
- This signature supports the involvement of systemic oxidative stress and inflammation in WMH pathogenesis.
- Findings suggest potential roles for oligodendrocyte proliferation and axon repair in WMH consequences.
