Alzheimer amyloid-β peptides block the activation of C/EBPβ and C/EBPδ in glial cells

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-β (Aβ) peptides on C/EBPβ and C/EBPδ, previously shown to be induced by inflammatory stimuli in glial cells. Surprisingly, electrophoretic mobility shift assay showed that both Aβ(1–42) and Aβ(25–35) blocked C/EBP activation induced by the inflammatory cytokine interleukin-1β (IL-1β) or lipopolysaccharide (LPS) in mixed primary glial cell cultures from rat. Aβ also blocked IL-1β- or LPS-induced C/EBP protein levels. The most prominent effects were observed on DNA binding activity and protein levels of C/EBPδ. Our results demonstrate a dysregulation of C/EBP when glial cells are activated in the presence of Alzheimer Aβ peptides.