Human Gene Set: WU_ALZHEIMER_DISEASE_DN


Standard name WU_ALZHEIMER_DISEASE_DN
Systematic name M13334
Brief description Genes down-regulated in brain endothelial cells from patients with Alzheimer disease.
Full description or abstract Neurovascular dysfunction substantially contributes to Alzheimer disease. Here, we show that transcriptional profiling of human brain endothelial cells (BECs) defines a subset of genes whose expression is age-independent but is considerably altered in Alzheimer disease, including the homeobox gene MEOX2 (also known as GAX), a regulator of vascular differentiation, whose expression is low in Alzheimer disease. By using viral-mediated MEOX2 gene silencing and transfer, we show that restoring expression of the protein it encodes, GAX, in BECs from individuals with Alzheimer disease stimulates angiogenesis, transcriptionally suppresses AFX1 forkhead transcription factor-mediated apoptosis and increases the levels of a major amyloid-beta peptide (Abeta) clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP), at the blood-brain barrier. In mice, deletion of Meox2 (also known as Gax) results in reductions in brain capillary density and resting cerebral blood flow, loss of the angiogenic response to hypoxia in the brain and an impaired Abeta efflux from brain caused by reduced LRP levels. The link of MEOX2 to neurovascular dysfunction in Alzheimer disease provides new mechanistic and therapeutic insights into this illness.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16116430   Authors: Wu Z,Guo H,Chow N,Sallstrom J,Bell RD,Deane R,Brooks AI,Kanagala S,Rubio A,Sagare A,Liu D,Li F,Armstrong D,Gasiewicz T,Zidovetzki R,Song X,Hofman F,Zlokovic BV
Exact source Table 2S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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