Gene expression profiling in alzheimer's disease brain microvessels

Shu Wang, Uzma Qaisar, Xiangling Yin, Paula Grammas

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-β and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature.

Original languageEnglish
Pages (from-to)193-205
Number of pages13
JournalJournal of Alzheimer's Disease
Volume31
Issue number1
DOIs
StatePublished - 2012

Keywords

  • Alzheimer's disease
  • brain
  • gene expression profile
  • microarray
  • microvessel

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