| First Author | Hong S | Year | 2014 |
| Journal | Neuron | Volume | 82 |
| Issue | 2 | Pages | 308-19 |
| PubMed ID | 24685176 | Mgi Jnum | J:261281 |
| Mgi Id | MGI:6109685 | Doi | 10.1016/j.neuron.2014.02.027 |
| Citation | Hong S, et al. (2014) Soluble Abeta oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes. Neuron 82(2):308-19 |
| abstractText | Soluble Abeta oligomers contribute importantly to synaptotoxicity in Alzheimer''s disease, but their dynamics in vivo remain unclear. Here, we found that soluble Abeta oligomers were sequestered from brain interstitial fluid onto brain membranes much more rapidly than nontoxic monomers and were recovered in part as bound to GM1 ganglioside on membranes. Abeta oligomers bound strongly to GM1 ganglioside, and blocking the sialic acid residue on GM1 decreased oligomer-mediated LTP impairment in mouse hippocampal slices. In a hAPP transgenic mouse model, substantial levels of GM1-bound Abeta(4)(2) were recovered from brain membrane fractions. We also detected GM1-bound Abeta in human CSF, and its levels correlated with Abeta(4)(2), suggesting its potential as a biomarker of Abeta-related membrane dysfunction. Together, these findings highlight a mechanism whereby hydrophobic Abeta oligomers become sequestered onto GM1 ganglioside and presumably other lipids on neuronal membranes, where they may induce progressive functional and structural changes. |
