CCAAT/enhancer binding protein δ (C/EBPδ) expression and elevation in Alzheimer’s disease

The CCAAT-enhancer binding protein (C/EBP) family of transcription factors, particularly C/EBPδ, is well known to regulate or co-regulate a wide range of inflammatory mediators and mechanisms in the periphery, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). These cytokines, in turn, can induce C/EBPδ expression and translocation to the nucleus as an active transcription factor. Because IL-1, IL-6, and TNF-α are increased in pathologically vulnerable regions of the Alzheimer’s disease (AD) brain, we sought to determine if C/EBPδ might be expressed in AD cortex. Immunohistochemistry of AD tissue sections revealed profuse C/EBPδ staining of astrocytes, particularly reactive astrocytes surrounding amyloid β peptide deposits. Substantially less immunoreactivity was observed in comparable sections from nondemented elderly control (ND) patients. These qualitative findings were consistent with quantitative Western blot densitometry results showing significant increases in C/EBPδ in AD compared to ND cortex samples. Additional in vitro studies were pursued in order to characterize functional activity of C/EBPδ in human elderly astrocytes. Consistent with a functionally active transcription factor, C/EBPδ immunoreactivity predominated in the nucleus of cultured AD and ND astrocytes, and exhibited increases and nuclear localization, as determined by Western blots and electrophoretic mobility shifts after exposure to C/EBPδ-inducing cytokines.