| First Author | Kam TI | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 7 | Pages | 2791-802 |
| PubMed ID | 23921129 | Mgi Jnum | J:201623 |
| Mgi Id | MGI:5514474 | Doi | 10.1172/JCI66827 |
| Citation | Kam TI, et al. (2013) FcgammaRIIb mediates amyloid-beta neurotoxicity and memory impairment in Alzheimer's disease. J Clin Invest 123(7):2791-802 |
| abstractText | Amyloid-beta (Abeta) 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 Fcgamma receptor II-b (FcgammaRIIb) mediates Abeta neurotoxicity and neurodegeneration. We found that FcgammaRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Abeta. Neuronal FcgammaRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Abeta-induced cell death in vitro. Fcgr2b deficiency ameliorated Abeta-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Abeta. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcgammaRIIb in Abeta neurotoxicity, we demonstrated that soluble Abeta oligomers interact with FcgammaRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Abeta neurotoxicity. We conclude that FcgammaRIIb has an aberrant, but essential, role in Abeta-mediated neuronal dysfunction. |
