IDENTIFICATION AND CHARACTERIZATION OF A KAPPA-B REL BINDING-SITE IN THE REGULATORY REGION OF THE AMYLOID PRECURSOR PROTEIN GENE/

Several observations support the hypothesis that pathogenetic mechanis ms of beta amyloid formation in Alzheimer's disease may involve altera tions in amyloid precursor protein (APP) gene expression, In this rega rd, 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 preferent ially with p50-containing members of the family, In particular, p50 ho modimers and p50/p65 and p50/c-Rel heterodimers act as transcriptional activators at the APP kappa B site, Finally, the nuclear complex spec ifically binding to the APP kappa B sites proves to be an integral par t of neurons and lymphocytes.