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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

inflammation

gene expression

Alzheimer's disease

alpha 1-antichymotrypsin

Alzheimer's peptide (A beta 42)

astrocytes

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)