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Juliet Moncaster, Joy Ghosh, Tsuneya Ikezu, John Voss, Rajendra Gangalum, Srikant Sarangi, Carmela Abraham, Suraj Bhat, Patric Stanton, Lee Goldstein; αB-Crystallin secretion from astrocytes and its implications for Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5752.
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Alzheimer’s disease neuritic plaque in the brain is composed of amyloid-β (Aβ) and also contains low molecular weight chaperones including αB-crystallin. We investigated the hypotheses that αB-crystallin is secreted by astrocytes and might potentiate pathogenic protein aggregation by interacting with human amyloid-β in Alzheimer's disease.
Immunocytochemistry, immunogold electron microscopy, SDS-PAGE, immunoblotting, electrophysiology, cell and organotypic slice culture.
Immunohistochemical analysis of human Alzheimer’s disease brain revealed co-localization of human Aβ (hAβ), human αB-crystallin and activated astrocytes in neuritic plaques. We investigated the source of the αB-crystallin and hypothesized it to be the surrounding activated astrocytes. In order to address this, we studied an astrocytic cell line and rat primary astrocytes. We found that αB-crystallin was expressed and secreted by astrocytes. Furthermore, we demonstrate that the resulting αB-crystallin that accumulates around the neuritic plaques binds to hAβ and causes neurotoxicity to neuronal cells and impairs synaptic function.
We demonstrate that αB-crystallin is generated and secreted from astrocytes. Furthermore, our data show that the αB-crystallin binds to hAβ and enhances the toxicity of hAβ to both synaptic function and neuronal survival therefore playing a role in the pathogenesis of Alzheimer’s disease.
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