April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
αB-Crystallin Modulates Amyloid-β toxicity and impairs Synaptic Transmission
Author Affiliations & Notes
  • Juliet A Moncaster
    Psychiatry, Boston University, Boston, MA
  • Joy Ghosh
    Psychiatry, Boston University, Boston, MA
  • Rajendra K Gangalum
    Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Tsuneya Ikezu
    Alzheimer, Boston University, Boston, MA
  • Ann McKee
    Psychiatry, Boston University, Boston, MA
  • John Voss
    University of California, Davis, CA
  • Carmela Abraham
    Alzheimer, Boston University, Boston, MA
  • Patric K Stanton
    New York Medical College, Valhalla, NY
  • Suraj P Bhat
    Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Lee E Goldstein
    Psychiatry, Boston University, Boston, MA
  • Footnotes
    Commercial Relationships Juliet Moncaster, None; Joy Ghosh, None; Rajendra Gangalum, None; Tsuneya Ikezu, None; Ann McKee, None; John Voss, None; Carmela Abraham, None; Patric Stanton, None; Suraj Bhat, None; Lee Goldstein, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4055. doi:https://doi.org/
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      Juliet A Moncaster, Joy Ghosh, Rajendra K Gangalum, Tsuneya Ikezu, Ann McKee, John Voss, Carmela Abraham, Patric K Stanton, Suraj P Bhat, Lee E Goldstein; αB-Crystallin Modulates Amyloid-β toxicity and impairs Synaptic Transmission. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4055. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Alzheimer’s disease neuritic plaque is composed of amyloid-β (Aβ) and also contains low molecular weight chaperones including αB-crystallin. We investigated the hypothesis that these ubiquitous molecular chaperones might potentiate pathogenic protein aggregation by interacting with Aβ

Methods: Immunogold electron microscopy, SDS-page and immunoblotting, spectral reflectance imaging biosensor, electrophysiology, cell and organotypic slice culture.

Results: Immunohistochemical analysis of human Alzheimer’s disease brain revealed co-localization of human Aβ (hAβ) and human αB-crystallin in neuritic plaques. Immunohistochemistry and western blotting demonstrated that αB-crystallin is expressed and secreted from astrocytes. αB-crystallin potentiated cytotoxicity in neuroblastoma cells exposed to hAβ, and potentiated hAβ-mediated CA1 pyramidal neuron death in organotypic hippocampal slice cultures that retain more in vivo-like synaptic architecture. In studies of long-term potentiation (LTP), a form of activity-dependent long-term synaptic plasticity that is a leading candidate memory mechanism, αB-crystallin markedly enhanced hAβ42-induced impairment of LTP synaptic transmission in hippocampal slices.

Conclusions: Our data show that αB-crystallin is expressed and secreted by astrocytes, binds to hAβ and enhances its toxicity to both synaptic function and neuronal survival, probably by increasing the concentration of low molecular weight soluble hAβ complexes. These properties of αB-crystallin suggest an antagonistic pleiotropy that may be critical to the pathogenesis of Alzheimer’s disease.

Keywords: 488 crystallins • 636 pathobiology • 429 astrocyte  
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