Effects of Alzheimer's peptide and alpha 1-antichymotrypsin on astrocyte gene expression

Crystal Baker, Henrietta Nielsen, Lennart Minthon, H. T. Wright, Sally Chappell, John Okyere, Sean May, Kevin Morgan, Noor Kalsheker, Sabina Janciauskiene

Research output: Contribution to journalArticlepeer-review

10 Citations (SciVal)

Abstract

We employed gene array technology to investigate the effects of alpha 1-antichymotrypsin (ACT), soluble or fibrillar Alzheimer's peptide (A beta(1-42)) alone and the combination of ACT/A beta(1-42) on human astrocytes. Using a 1.2-fold change as significance threshold, 398 astrocyte genes showed altered expression in response to these treatments compared to controls. Of the 276 genes affected by the ACT/soluble A beta(1-42) combination, 195 (70.6%) were suppressed. The ACT/fibrillar A beta(1-42) combination affected expression of 64 genes of which 58 (90.5%) were up-regulated. The most prominent gene expression changes in response to the ACT/soluble A beta(1-42), were the down-regulation of at least 60 genes involved in transcription, signal transduction, apoptosis and neurogenesis. The ACT/fibril A beta(1-42) increased the expression of genes involved in transcription regulation and signal transduction. Surprisingly, gene expression of astrocytes exposed to soluble or fibrillar A beta(1-42) alone was largely unaffected. Thus, the molecular forms generated by the combination of ACT/A beta(1-42) alter expression of astrocyte genes more profoundly in breadth and magnitude than soluble or fibrillar A beta(1-42) alone, suggesting that pathogenic effects of A beta(1-42) may occur as a consequence of its association with other proteins. (c) 2005 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)51-61
JournalNeurobiology of Aging
Volume28
Issue number1
DOIs
Publication statusPublished - 2007

Subject classification (UKÄ)

  • Neurology
  • Rheumatology and Autoimmunity

Keywords

  • inflammation
  • gene expression
  • Alzheimer's disease
  • alpha 1-antichymotrypsin
  • Alzheimer's peptide (A beta 42)
  • astrocytes

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