Human Gene Set: BLALOCK_ALZHEIMERS_DISEASE_INCIPIENT_DN


Standard name BLALOCK_ALZHEIMERS_DISEASE_INCIPIENT_DN
Systematic name M6110
Brief description Genes down-regulated in patients at the incipient stage of Alzheimer's disease.
Full description or abstract The pathogenesis of incipient Alzheimer's disease (AD) has been resistant to analysis because of the complexity of AD and the overlap of its early-stage markers with normal aging. Gene microarrays provide new tools for addressing complexity because they allow overviews of the simultaneous activity of multiple cellular pathways. However, microarray data interpretation is often hindered by low statistical power, high false positives or false negatives, and by uncertain relevance to functional endpoints. Here, we analyzed hippocampal gene expression of nine control and 22 AD subjects of varying severity on 31 separate microarrays. We then tested the correlation of each gene's expression with MiniMental Status Examination (MMSE) and neurofibrillary tangle (NFT) scores across all 31 subjects regardless of diagnosis. These well powered tests revealed a major transcriptional response comprising thousands of genes significantly correlated with AD markers. Several hundred of these genes were also correlated with AD markers across only control and incipient AD subjects (MMSE > 20). Biological process categories associated with incipient AD-correlated genes were identified statistically (ease program) and revealed up-regulation of many transcription factor/signaling genes regulating proliferation and differentiation, including tumor suppressors, oligodendrocyte growth factors, and protein kinase A modulators. In addition, up-regulation of adhesion, apoptosis, lipid metabolism, and initial inflammation processes occurred, and down-regulation of protein folding/metabolism/transport and some energy metabolism and signaling pathways took place. These findings suggest a new model of AD pathogenesis in which a genomically orchestrated up-regulation of tumor suppressor-mediated differentiation and involution processes induces the spread of pathology along myelinated axons.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 14769913   Authors: Blalock EM,Geddes JW,Chen KC,Porter NM,Markesbery WR,Landfield PW
Exact source Web Table 6: Downregulated
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: Renamed from ALZHEIMERS_INCIPIENT_DN

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