Altered gene expression occurs in central nervous system disorders, including Alzheimer's disease (AD). Transcription factor Sp1 may be involved insofar as it can regulate the expression of several AD-related proteins, including amyloid precursor protein (APP) and tau. Sp1 could itself be regulated by inflammatory and other factors associated with AD, such as interleukin-1beta. We measured an almost threefold elevation in the number of mRNA molecules of this cytokine in the AD frontal cortex. Sp1 mRNA was found to be up-regulated in these AD brains (along with Sp1-regulated COX-2), and the Sp1 increase was also seen at the protein level by Western immunoblotting. To determine whether this would also occur in transgenic mice developing AD pathology, we examined the expression of Sp1 in the cortex and hippocampus and observed higher levels of Sp1 mRNA and protein. These results indicate that elements of regulatory pathways involving transcription factor Sp1 may be useful targets for therapeutic intervention to prevent or reverse AD.