Several observations support the hypothesis that pathogenetic mechanisms of beta amyloid formation in Alzheimer's disease may involve alterations in amyloid precursor protein (APP) gene expression. In this regard, molecular dissection of the APP gene transcriptional regulation is of primary importance. We report evidence that members of the family of transcription factors NF kappa B/Rel can specifically recognize two identical sequences located in the 5'-regulatory region of APP. These sequences, which we refer to as APP kappa B sites, interact preferentially with p50-containing members of the family. In particular, p50 homodimers and p50/p65 and p50/c-Rel heterodimers act as transcriptional activators at the APP kappa B site. Finally, the nuclear complex specifically binding to the APP kappa B sites proves to be an integral part of neurons and lymphocytes.