Abstract Details

Title Decoding Pathophysiological Mechanisms of Cerebral Small-Vessel Disease by Gene Expression Analysis in Human Brain Tissues

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S32 - (-)

Poster/Presentation
Number 002

Objective

Background SVD is a common condition in older people and contributes to the development of vascular dementia (VaD), and lacunar strokes. A limited number of studies of its genetic basis have been performed so far and the etiology of the disease remains elusive.

Design/Methods We analysed the gene expression of post-mortem brain specimen of the frontal cortex, thalamus and frontal white matter of 5 patients histopathologically diagnosed with SVD in comparison with 5 non-affected patients, using oligonucleotide-based microarray technology (Affymetrix® Genechips). Gene annotation and statistic analysis were performed using Partek® Genomics Suite. Genes with fold expression change (F) <-1.5 or >1.5, and P<0.01 were considered differently expressed between SVD and control groups. Clustering of the genes was performed using DAVID® bioinformatics resources. Immunohistological staining of brain sections were used to confirm gene expression results.

Results Classification into functional groups revealed that genes differentially expressed in the three brain regions were involved in the ubiquitin-mediated proteolysis, cell adhesion, cell cycle, anti-oxidative and fatty acid metabolisms. Genes involved in apoptosis and platelet aggregation were found differently expressed in the cortex and thalamus. Genes involved in myelination, angiogenesis and vesicular transport were differently expressed specifically in the cortex, whereas the expression of genes involved in glycolysis and nitrogen metabolisms was different in the white matter.

Conclusions Brains of patients suffering from SVD revealed that, on a molecular level, chronic SVD follows patterns of neurodegenerative and metabolic disorders more than ischemic ones. These results may provide guide to potential neuroprotective strategies for prevention of SVD in patients at risk.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Leo Bonati, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stefan T. Engelter, MD (University Hospital Neurology Clinic)	No disclosure on file
	No disclosure on file
Philippe A. Lyrer, MD (University Hospital Basel)	No disclosure on file

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