Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain

Huichun Xu, Boryana Stamova, Glen Clifford Jickling, Yingfang Tian, Xinhua Zhan, Bradley P. Ander, Dazhi Liu, Renée Turner, Jonathan Rosand, Larry B. Goldstein, Karen L. Furie, Piero Verro, S. Claiborne Johnston, Frank R. Sharp, Charles S. Decarli

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2744-2749
Number of pages6
Issue number12
StatePublished - Dec 2010


  • Alzheimer disease
  • blood
  • gene expression profiling
  • inflammation
  • ischemia
  • oxidative stress
  • white matter

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing


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