title: Gene expression profiling in Alzheimer's disease brain microvessels.
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.
authors.affiliation: Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Uzma
authors.initials: U
authors.lastname: Qaisar
authors.forename: Xiangling
authors.initials: X
authors.lastname: Yin
authors.forename: Paula
authors.initials: P
authors.lastname: Grammas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016207:Cytokines