REGULATION OF BETA-AMYLOID PRECURSOR PROTEIN ISOFORM MESSENGER-RNAS BY TRANSFORMING GROWTH-FACTOR-BETA-1 AND INTERLEUKIN-1-BETA IN ASTROCYTES

In cultured astrocytes, all three major transcripts of beta-amyloid precursor protein (APP) were expressed with the ratio for APP695, APP751 and APP770 isoform mRNAs being 1:4:2, In comparison with controls, treatment of astrocytes with transforming growth factor-beta1 (TGF-beta1) produced about 6 fold increase in total APP mRNA, while elevation in the interleukin-1beta (IL-1beta) treated group was small and may relate to the mitogenic effect of IL-1beta on astrocytes. Treatment of astrocytes with cytokines also produced marked changes in the upregulation in expression of different APP isoforms. The net increase in mRNAs of KPI-containing isoforms APP751 and APP770 was relatively more than for the APP695 isoform. This phenomenon was mainly related to the differences in the expression of KPI-containing APP isoforms and APP695 isoform in the controls. The present findings provide further evidence for the involvement of astrocytes in a cascade of events leading to the development of senile plaques in Alzheimer's disease and Down's syndrome.