Suppression of Alzheimer Amyloid Precursor Protein (APP) Expression by Exogenous APP mRNA

To establish a cell line expressing enhanced levels of β-amyloid precursor protein (β-APP), we constructed plasmid DNAs expressing β-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 β-APP iso-mRNAs, we have made the unexpected observation that enhanced expression of β-APP-751 mRNA resulted in a significant reduction of β-APP-770 and -695 mRNA levels. Suppression of β-APP-770 and -695 mRNA was also observed in cells expressing truncated and chimeric β-APP-751 mRNAs. Similar observations were made in P19 cells expressing a chimeric β-APP-751 mRNA where endogenous β-APP-751 mRNA levels also were decreased. Also, suppression of β-APP-770 and -751 mRNAs was observed in human kidney cells expressing exogenous β-APP-695 mRNA.