RGD Reference Report - Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: implications for disease pathogenesis. - Rat Genome Database

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Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: implications for disease pathogenesis.

Authors: Grammas, P  Samany, PG  Thirumangalakudi, L 
Citation: Grammas P, etal., J Alzheimers Dis. 2006 Mar;9(1):51-8.
RGD ID: 9068875
Pubmed: PMID:16627934   (View Abstract at PubMed)

The notion that microvascular abnormalities contribute to deleterious changes in the Alzheimer's disease (AD) brain is supported by work from our laboratory and others demonstrating biochemical and functional alterations of the microcirculation in AD. The objective of this study is to determine whether levels of neurotoxic (thrombin) and inflammatory (interleukin 8 (IL-8), integrins alphaVbeta3 and alphaVbeta5) proteins are altered in microvessels isolated from AD patients compared to levels in vessels obtained from non-demented age-matched controls. We also evaluate in AD and control microvessels expression of the transcription factor hypoxia-inducible factor 1-alpha(HIF1-alpha), which regulates pro-inflammatory gene expression, and the regulation of HIF1-alpha expression by thrombin in cultured brain endothelial cells. Our results indicate that in AD there are high levels of expression of the neurotoxic protease thrombin and the inflammation-associated proteins IL-8 and alphaVbeta3 and alphaVbeta5 integrins. HIF1-alpha is higher in AD microvessels compared to control and thrombin treatment of cultured brain endothelial cells results in increased expression of HIF1-alpha. These data suggest that in AD the cerebral microcirculation is a source of neurotoxic and inflammatory mediators and as such contributory to pathologic processes ongoing in the AD brain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IEP 9068875mRNA more ...RGD 
Alzheimer's disease  ISOHIF1A (Homo sapiens)9068875; 9068875mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information