%0 Journal Article
%A Moncaster, Juliet A
%A Ghosh, Joy
%A Gangalum, Rajendra K
%A Ikezu, Tsuneya
%A McKee, Ann
%A Voss, John
%A Abraham, Carmela
%A Stanton, Patric K
%A Bhat, Suraj P
%A Goldstein, Lee E
%T αB-Crystallin Modulates Amyloid-β toxicity and impairs Synaptic Transmission
%B Investigative Ophthalmology & Visual Science
%D 2014
%J Investigative Ophthalmology & Visual Science
%V 55
%N 13
%P 4055-4055
%@ 1552-5783
%X  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 Immunogold electron microscopy, SDS-page and immunoblotting, spectral reflectance imaging biosensor, electrophysiology, cell and organotypic slice culture. 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. 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. 
%[ 4/12/2021