BETA-A AMYLOID PEPTIDE (25-35) INDUCED APP EXPRESSION IN CULTURED ASTROCYTES

Alzheimer's disease is characterized by an accumulation of senile or n euritic plaques surrounded by activated microglia and reactive astrocy tes, the cell processes of which are frequently in contact with the am yloid core, The major component of this amyloid deposit is the amyloid peptide (beta A or beta A4), These reactive glia are characterized by their hypertrophic phenotype and by the overexpression of some molecu les such as glial fibrillary acidic protein and the amyloid precursor protein (APP), The purpose of this work was to analyze whether APP exp ression was modified in astrocytes by the presence of PA peptide. To s tudy this, the effects of beta-Amyloid (25-35) on cultured astrocytes were analyzed and compared with those of a scrambled peptide. Our data indicated that the addition of previously polymerized beta A peptide induced a marked morphological change from a hat, polygonal shape to a stellated, process-bearing morphology, This change occurred with an i ncrease in APP immunoreactivity that is dependent of phosphatases PP2A or PP1, since it was inhibited by okadaic acid. Upregulation of APP p rotein expression appears to be mainly nontranscriptional, because the increase of APP protein precedes the increase of mRNA expression. The analysis of several APP isoforms indicated that this increment is not due to changes of a single isoform, Our data may correlate with some in vivo reports of astrocytic APP induction after brain insult, sugges ting an important role for beta A peptide in the initial process and/o r maintenance of the reactive phenotype in vivo. (C) 1998 Wiley-Liss,I nc.