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A\u03b2 disrupts AMPA receptor-mediated synaptic plasticity, a key factor in early AD progression. Numerous studies propose that A\u03b2 oligomers hinder synaptic plasticity, particularly long-term potentiation (LTP), by disrupting GluA1 (encoded by GRIA1) function, although the precise mechanism remains unclear. In this study, we demonstrate that A\u03b2 mediates the accumulation of GM1 ganglioside in lipid raft domains of cultured cells, and GluA1 exhibits preferential localization in lipid rafts via direct binding to GM1. A\u03b2 enhances the raft localization of GluA1 by increasing GM1 in these areas. Additionally, chemical LTP stimulation induces lipid raft-dependent GluA1 internalization in A\u03b2-treated neurons, resulting in reduced cell surface and postsynaptic expression of GluA1. Consistent with this, disrupting lipid rafts and GluA1 localization in rafts rescues A\u03b2-mediated suppression of hippocampal LTP. These findings unveil a novel functional deficit in GluA1 trafficking induced by A\u03b2, providing new insights into the mechanism underlying AD-associated cognitive dysfunction.<\/jats:p>","DOI":"10.1242\/jcs.261281","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T13:20:31Z","timestamp":1714137631000},"source":"Crossref","is-referenced-by-count":7,"title":["A\u03b2 peptide enhances GluA1 internalization via lipid rafts in Alzheimer's-related hippocampal LTP dysfunction"],"prefix":"10.1242","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5163-7744","authenticated-orcid":false,"given":"Ryosuke","family":"Midorikawa","sequence":"first","affiliation":[{"name":"University of Miyazaki 1 Department of Neuroscience, Faculty of Medicine , , Miyazaki 889-1692 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Wakazono","sequence":"additional","affiliation":[{"name":"University of Miyazaki 1 Department of Neuroscience, Faculty of Medicine , , Miyazaki 889-1692 , Japan"},{"name":"Frontier Science Research Center, University of Miyazaki 2 Laboratory of Biophysical Research , , Miyazaki 889-1692 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-6307","authenticated-orcid":false,"given":"Kogo","family":"Takamiya","sequence":"additional","affiliation":[{"name":"University of Miyazaki 1 Department of Neuroscience, Faculty of Medicine , , Miyazaki 889-1692 , Japan"},{"name":"Frontier Science Research Center, University of Miyazaki 2 Laboratory of Biophysical Research , , Miyazaki 889-1692 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"2024042613202453900_JCS261281C1","doi-asserted-by":"publisher","first-page":"4598","DOI":"10.1523\/JNEUROSCI.0325-07.2007","article-title":"Conservation of glutamate receptor 2-containing AMPA receptors during long-term potentiation","volume":"27","author":"Adesnik","year":"2007","journal-title":"J. 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