Skip to main content

Advertisement

You are viewing the new article page. Let us know what you think. Return to old version

Poster presentation | Open | Published:

FcgRIIb mediates amyloid-β neurotoxicity and memory impairment in a model of Alzheimer’s disease

Amyloid-β (Aβ) induces neuronal loss and cognitive deficits and is believed to be a prominent cause of Alzheimer’s disease (AD). However, the cellular mechanism of the pathogenesis is not fully understood. Here we report that Fcg-receptor IIb (FcgRIIb) mediates Aβ neurotoxicity and neurodegeneration. We found that FcgRIIb is significantly up-regulated in the hippocampus of AD brains and neuronal cells exposed to Aβ1-42. Neuronal FcgRIIb activates ER stress and caspase-12, and FcgRIIb knockout primary neurons are resistant to Aβ1-42-induced cell death in vitro. FcgRIIb deficiency ameliorates Aβ1-42-induced inhibition of long-term potentiation and inhibits the reduction of synaptic density by naturally secreted Aβ. Moreover, genetic depletion of FcgRIIb rescues the memory impairments in AD model mice. In an action mode of FcgRIIb in Aβ neurotoxicity, we found that soluble Aβ1-42 oligomers interact with FcgRIIb in vitro and in AD brains, and inhibition of their interaction blocks Aβ1-42 neurotoxicity. Thus, we conclude that FcgRIIb has an aberrant but essential role in Aβ1-42-mediated neuronal dysfunction, providing insight into Aβ neuropathology.

Author information

Correspondence to Yong-Keun Jung.

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Memory Impairment
  • Primary Neuron
  • Neuronal Dysfunction
  • Synaptic Density
  • Genetic Depletion