Document Detail


Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain.
MedLine Citation:
PMID:  20966416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Huichun Xu; Boryana Stamova; Glen 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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-21
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  41     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2010-12-22     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2744-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Alzheimer Disease / genetics,  metabolism,  pathology
Brain / pathology*
Cluster Analysis
Female
Hormones / physiology
Humans
Inflammation / pathology
Magnetic Resonance Imaging
Male
Microarray Analysis
Oxidative Stress / genetics,  physiology
Principal Component Analysis
RNA / biosynthesis*,  blood*,  genetics
Signal Transduction / genetics,  physiology
Grant Support
ID/Acronym/Agency:
P30 AG010129/AG/NIA NIH HHS; P30 AG010129-19/AG/NIA NIH HHS; P30 AG10129/AG/NIA NIH HHS; R01 AG021028/AG/NIA NIH HHS; R01 AG021028/AG/NIA NIH HHS; R01 AG021028-07/AG/NIA NIH HHS; R01 AG042292/AG/NIA NIH HHS; R01 NS056302/NS/NINDS NIH HHS; UL1 RR024131/RR/NCRR NIH HHS; UL1 RR024131/RR/NCRR NIH HHS; UL1 RR024131-04/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Hormones; 63231-63-0/RNA
Comments/Corrections

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