Apolipoprotein E Isoforms Differentially Regulate Amyloid-β Stimulated Inflammation in Rat and Mouse Astrocytes

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Title: Apolipoprotein E Isoforms Differentially Regulate Amyloid-β Stimulated Inflammation in Rat and Mouse Astrocytes
Authors: Dorey, Evan J
Date: 2012
Abstract: Neuroinflammation occurs in Alzheimer’s disease (AD) brain, and plays a role in neurodegeneration. The main aim of this study was to determine how treatments with exogenous apolipoprotein E (ApoE2, E3 and E4 isoforms), a genetic risk factor for AD, affects the amyloid-β (Aβ) induced inflammatory response in vitro in astrocytes. Recombinant, lipid-free ApoE4 was found not to affect Aβ-induced inflammation in rat astrocytes, while ApoE2 showed a protective effect. Mouse cells expressing human ApoE isoforms, which have similar lipidation and modification to native human ApoE, showed ApoE4 promoting inflammation, and no ApoE2 protective effect upon Aβ treatment. A Protein/DNA array was used to screen 345 transcription factors in rat astrocytes treated with Aβ and/or ApoE isoforms, in order to determine which contribute to the observed ApoE2 protection. Some candidates were validated by Western Blot or EMSA and/or by inhibition or activation. The findings suggest ApoE isoforms differentially regulate Aβ-induced inflammation, and multiple signalling pathways are involved in the process.
URL: http://hdl.handle.net/10393/23581
http://dx.doi.org/10.20381/ruor-6258
CollectionThèses, 2011 - // Theses, 2011 -
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