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Beta-amyloid expression, release and extracellular deposition in aged rat brain slices

Molecular Psychiatry volume 13, pages 939–952 (2008)Cite this article

Abstract

Alzheimer's disease (AD) is characterized by β-amyloid plaques, tau pathology, cholinergic cell death and inflammation. The aim of this study was to investigate whether β-amyloid is generated, released and extracellularly deposited in organotypic brain slices. In developing slices, no amyloid-precursor protein (APP) was detectable; however, there was a strong upregulation in aging slices. In such slices, rat β-amyloid(1–42) and -(1–40) peptides were found using four sequence-specific antibodies. APP and β-amyloid were expressed in neurons and to a lesser extent in astrocytes. Beta-amyloid was secreted into the medium. Beta-amyloid was located extracellularly when aging slices were incubated with medium at pH 6.0 including apolipoprotein E4 (ApoE4). It is concluded that aging organotypic brain slices express β-amyloid and that acidosis induces cell death with efflux of β-amyloid and extracellular depositions, which is triggered by ApoE4. This novel in vitro model may enable us to investigate further the pathological cascade for AD and may be useful to explore future therapeutics.

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Acknowledgements

This study was supported by the Austrian Science Fund (P16130-B08 and P19122-B05). We thank Iris Berger, Michael Pirchl and Ursula Kirzenberger-Winkler for excellent technical help. We also thank Dr Georg Wietzorrek for help with the confocal microscopy.

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  1. Department of General Psychiatry, Laboratory of Psychiatry and Exp. Alzheimer's Research, Innsbruck Medical University, Innsbruck, Austria

    J Marksteiner & C Humpel

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Correspondence to C Humpel.

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The authors declare that they have no competing financial interests.

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Marksteiner, J., Humpel, C. Beta-amyloid expression, release and extracellular deposition in aged rat brain slices. Mol Psychiatry 13, 939–952 (2008). https://doi.org/10.1038/sj.mp.4002072

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