Alzheimer's disease is associated with the accumulation of amyloid-beta (Abeta) in the brain and has been linked to memory loss and neuronal degeneration. Tae-In Kam and colleagues report that IgG receptor FCgammaRIIb mediates Abeta neurotoxicity and neurodegeneration. FcgammaRIIb was significantly up regulated in the hippocampus of AD brains and Abeta exposure activated stress and death pathways and inhibited long-term potentiation (an enhancement in communication between two neurons) in a FCgammaRIIb-dependent manner. Moreover, Fcgr2b depletion ameliorated memory impairments in a mouse model of AD, demonstrating that FCgammaRIIb is essential for Abeta-induced neurotoxicity. In the accompanying image, cultured hippocampal neurons express a fluorescent protein, allowing for the visualization of dendritic spines by microscopy. Kam and colleagues compared the effects of Abeta treatment in wildtype neurons (two left panels, right panel treated with Abeta) and neurons lacking FCgammaRIIb (two right panels, right panel treated with Abeta). In the absence of FCgammaRIIb, Abeta did not alter spine density.
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 pathology of the disease is not fully understood. Here, we report that IgG Fcγ receptor II-b (FcγRIIb) mediates Aβ neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aβ. Neuronal FcγRIIb activated ER stress and caspase-12, and
Tae-In Kam, Sungmin Song, Youngdae Gwon, Hyejin Park, Ji-Jing Yan, Isak Im, Ji-Woo Choi, Tae-Yong Choi, Jeongyeon Kim, Dong-Keun Song, Toshiyuki Takai, Yong-Chul Kim, Key-Sun Kim, Se-Young Choi, Sukwoo Choi, William L. Klein, Junying Yuan, Yong-Keun Jung