Inhibition of the NGF and IL-1 beta-induced expression of Alzheimer's amyloid precursor protein by antisense oligonucleotides

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain chara cterized by the extracellular deposition of amyloid in senile plaques and a long the walls of the cerebral vasculature. The principal constituent of am yloid deposit is amyloid beta peptide (AP) derived from its larger precurso r protein, amyloid precursor protein (APP). The overexpression of APP is kn own to be a risk factor for AP deposit in AD and in Down syndrome (DS). The inhibition of APP expression has been thought to be beneficial to patients with AD and DS. In this study, we investigated the effects of antisense ol igonucleotide (AO) on the overexpression of APP induced by IL-1 beta and NG F. Using phosphorothioate-oligonucleotides against initiation codon significan tly reduced the protein levels of APP induced by NGF and IL-1 beta to basal level in PC12 cell culture systems. These results showed that these antise nse oligonucleotides may have a potential to be a therapeutic agent for som e patients with AD and DS.