SUPPRESSION OF ALZHEIMER AMYLOID PRECURSOR PROTEIN (APP) EXPRESSION BY EXOGENOUS APP MESSENGER-RNA

To establish a cell line expressing enhanced levels of beta-amyloid pr ecursor protein (beta-APP), we constructed plasmid DNAs expressing bet a-APP-751 mRNA and transfected them into COS-1 cells. Using a modified version of the reverse transcriptase polymerase chain reaction which is RNA sensitive to study the beta-APP iso-mRNAs, we have made the une xpected observation that enhanced expression of beta-APP-751 mRNA resu lted in a significant reduction of beta-APP-770 and -695 mRNA levels, Suppression of beta-APP-770 and -695 mRNA was also observed in cells e xpressing truncated and chimeric beta-APP-751 mRNAs, Similar observati ons were made in P19 cells expressing a chimeric beta-APP-751 mRNA whe re endogenous beta-APP-751 mRNA levels also were decreased. Also, supp ression of beta-APP-770 and -751 mRNAs was observed in human kidney ce lls expressing exogenous beta-APP-695 mRNA. (C) 1996 Academic Press, I nc.