Members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors have been reported to be up-regulated in Alzheimer's disease. In the present study, we have investigated the effects of amyloid-beta (A beta) peptides on C/EBP beta and C/EBP delta, previously shown to be induced by inflammatory stimuli in glial cells. Surprisingly, electrophoretic mobility shift assay showed that both A beta(1-42) and A beta(25-35) blocked C/EBP activation induced by the inflammatory cytokine interleukin-1 (IL-1 beta) or lipopolysac-charicle (LPS) in mixed primary glial cell cultures from rat. A beta also blocked IL-1 or LPS-incluced C/EBP protein levels. The most prominent effects were observed on DNA binding activity and protein levels of C/EBP delta. Our results demonstrate a dysregulation of C/EBP when glial cells are activated in the presence of Alzheimer A beta peptides. (c) 2008 Elsevier Inc. All rights reserved.