{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:18:44Z","timestamp":1790659124927,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Synaptic and extrasynaptic distribution of N\u2010methyl\u2010D\u2010aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer\u00b4s disease (AD) subjects, despite their\u00a0contribution to neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as\u00a0post\u2010translational modifications, such as phosphorylation and glycosylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Lower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Reduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>New protocol to isolate synaptic and extrasynaptic membranes from the human cortex.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Low GluN2B and GluN2A levels in Alzheimer\u00b4s disease (AD) synaptic membranes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>High GluN2B and GluN1 levels in AD extrasynaptic membranes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Specific glycoforms of extrasynaptic GluN2B and GluN2A.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Low phosphorylation at Tyr1472 in synaptic GluN2B in AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14125","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T06:29:09Z","timestamp":1729837749000},"page":"8231-8245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients"],"prefix":"10.1002","volume":"20","author":[{"given":"Sergio","family":"Escamilla","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2010Consejo Superior de Investigaciones Cient\u00edficas (UMH\u2010CSIC)  Sant Joan d'Alacant Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (Ciberned)  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (Isabial)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Badillos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (Ciberned)  Madrid Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular School of Medicine Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan X.","family":"Comella","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (Ciberned)  Madrid Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular School of Medicine Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u Hospital Sant Joan de D\u00e9u  Esplugues de Llobregat Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Sol\u00e9","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (Ciberned)  Madrid Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular School of Medicine Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra (Barcelona) Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"P\u00e9rez\u2010Ota\u00f1o","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2010Consejo Superior de Investigaciones Cient\u00edficas (UMH\u2010CSIC)  Sant Joan d'Alacant Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose V. 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