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BetaA amyloid peptide (25-35) induced APP expression in cultured astrocytes
M T Moreno-Flores1, O Salinero, F Wandosell
1Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco-Madrid, Spain.
Abstract:
Alzheimer's disease is characterized by an accumulation of senile or neuritic plaques surrounded by activated microglia and reactive astrocytes, the cell processes of which are frequently in contact with the amyloid core. The major component of this amyloid deposit is the amyloid peptide (betaA or betaA4). These reactive glia are characterized by their hypertrophic phenotype and by the overexpression of some molecules such as glial fibrillary acidic protein and the amyloid precursor protein (APP). The purpose of this work was to analyze whether APP expression was modified in astrocytes by the presence of betaA peptide. To study 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 betaA peptide induced a marked morphological change from a flat, polygonal shape to a stellated, process-bearing morphology. This change occurred with an increase in APP immunoreactivity that is dependent of phosphatases PP2A or PP1, since it was inhibited by okadaic acid. Upregulation of APP protein 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, suggesting an important role for betaA peptide in the initial process and/or maintenance of the reactive phenotype in vivo.
Insights
Alzheimer's disease involves amyloid plaques and reactive astrocytes. Beta-amyloid peptide (betaA) exposure in cultured astrocytes caused morphological changes and increased amyloid precursor protein (APP) expression, suggesting betaA
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Alzheimer's disease (AD) is marked by amyloid plaques, composed mainly of amyloid beta peptide (betaA).
- Reactive astrocytes and microglia surround these plaques, exhibiting altered phenotypes and overexpressing proteins like amyloid precursor protein (APP).
Purpose of the Study:
- To investigate if betaA peptide influences APP expression in astrocytes.
- To analyze the effects of beta-Amyloid (25-35) on cultured astrocytes and compare them to a scrambled peptide control.
Main Methods:
- Cultured astrocytes were treated with polymerized beta-amyloid (25-35) peptide or a scrambled control peptide.
- Morphological changes and APP immunoreactivity were assessed.
- The role of phosphatases PP2A/PP1 was evaluated using okadaic acid.
- APP protein and mRNA levels were quantified to determine the transcriptional or non-transcriptional nature of the upregulation.
Main Results:
- Beta-amyloid peptide induced significant morphological changes in astrocytes, shifting them from a polygonal to a stellated, process-bearing shape.
- APP immunoreactivity increased following betaA exposure, an effect inhibited by okadaic acid, indicating dependence on phosphatases PP2A/PP1.
- APP protein upregulation was primarily non-transcriptional, as protein levels rose before mRNA levels.
- The increase in APP expression was not attributed to a single APP isoform.
Conclusions:
- Beta-amyloid peptide directly impacts astrocyte morphology and APP expression.
- The findings suggest a non-transcriptional mechanism for APP upregulation in astrocytes stimulated by betaA.
- These results support the in vivo observation of astrocytic APP induction following brain injury and highlight betaA's role in reactive astrogliosis.