{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:29:55Z","timestamp":1785493795729,"version":"3.56.0"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>N\u2010methyl\u2010D\u2010aspartate receptors (NMDARs) are glutamate\u2010binding calcium channels that play a key role in brain function and have been linked to many neurological disorders. NMDARs are multi\u2010pass membrane heterotetrameric complexes composed of two compulsory GluN1 subunits and two GluN2 (A\u2010D) or GluN3 (A\u2010B) subunits, from which GluN1, GluN2B, GluN2A, and GluN3A are widely expressed in the adult brain. This study assesses the presence of GluN1, GluN2B, GluN2A, and GluN3A in the cerebrospinal fluid (CSF) from healthy individuals, viral and autoimmune encephalitis, Huntington's disease (HD) and Alzheimer's disease (AD) patients. Samples were run in SDS\u2010PAGE under reducing conditions and resolved with different anti\u2010ectodomain and anti\u2010C\u2010terminal antibodies that combined with immunoprecipitation analyses, served to demonstrate the presence of full\u2010length GluN1, GluN2A, GluN2B, and GluN3A in CSF. These NMDAR subunit complexes are not associated with extracellular vesicles. As a proof of concept of the identity of NMDAR subunits in the CSF, we demonstrated reduced levels of GluN1 in the CSF from patients with autoimmune encephalitis caused by anti\u2010GluN1 antibodies compared with other causes of encephalitis; and showed a depletion of CSF GluN3A in a <jats:italic>Grin3a<\/jats:italic> knockout mouse model. Moreover, we observed higher GluN3A levels in CSF in both asymptomatic and symptomatic HD patients; while GluN2A levels were lower in CSF from AD patients. In conclusion, here we demonstrate the presence of NMDAR full\u2010length subunits in CSF and that changes in NMDAR subunits balance could serve to identify alterations related to pathological conditions.<\/jats:p>","DOI":"10.1111\/jnc.70192","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T10:34:54Z","timestamp":1755513294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Alterations of <scp>NMDAR<\/scp> Subunits in the Cerebrospinal Fluid Across Neurodegenerative and Immunological Disorders"],"prefix":"10.1111","volume":"169","author":[{"given":"Sergio","family":"Escamilla","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Alicante Universidad Miguel Hern\u00e1ndez\u2010CSIC, Sant Joan d' Alacant  Alicante Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de 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":"Roc\u00edo","family":"P\u00e9rez\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante Universidad Miguel Hern\u00e1ndez\u2010CSIC, Sant Joan d' Alacant  Alicante Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de 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":"Carmen","family":"M\u00e1rquez\u2010Marco","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante Universidad Miguel Hern\u00e1ndez\u2010CSIC, Sant Joan d' Alacant  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Camporesi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Brinkmalm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Padovani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Continuity of Care and Frailty Neurology Unit, ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Brain Health Center University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pilotto","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Continuity of Care and Frailty Neurology Unit, ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tolassi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Continuity of Care and Frailty Neurology Unit, ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Arici","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Continuity of Care and Frailty Neurology Unit, ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Volonghi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Continuity of Care and Frailty Neurology Unit, ASST Spedali Civili Hospital  Brescia Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease Institute of Neurology, University College London  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Paris Brain Institute, ICM, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne University  Paris France"},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"P\u00e9rez\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Movement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Biomedical Research Institute Sant Pau (IIB\u2010Sant Pau)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Kulisevsky","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Movement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Biomedical Research Institute Sant Pau (IIB\u2010Sant Pau)  Barcelona Spain"},{"name":"Department of Medicine Autonomous University of Barcelona  Barcelona Spain"},{"name":"European Huntington's Disease Network (EHDN)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Cuchillo\u2010Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante Universidad Miguel Hern\u00e1ndez\u2010CSIC, Sant Joan d' Alacant  Alicante Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-320X","authenticated-orcid":false,"given":"Javier","family":"S\u00e1ez\u2010Valero","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante Universidad Miguel Hern\u00e1ndez\u2010CSIC, Sant Joan d' Alacant  Alicante Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL)  Alicante Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010014\u20100088\u20104"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17101265"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12816"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280879"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101326\u201010\u20102"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2012.02057.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/30748"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010021\u201002107\u20100"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.05.002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14125"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251810220"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.12.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051\u20105960\u20101\u201046"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201002841\u20107"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108551"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0064\u201012.2012"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112477"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(06)70355\u20106"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2911"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u20102007\u201011113"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107321\u20107_13"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13548"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf093"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.001290"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010019\u201001677\u20108"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00125"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.12.012"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.12.021"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3246"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.05.013"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13413"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100297\u2010y"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.374397"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2011.07628.x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3504"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.03.030"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa052"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000823R"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1680"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa609"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010024\u201001529\u20101"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(01)00539\u20106"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858411435129"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.03.045"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004743"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010018\u20101255\u20109"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12355"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv346"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858406294270"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169\u2010328x(00)00111\u2010x"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022\u20103042.2001.00736.x"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700624200"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010016\u20102546\u20105"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31232"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:34:00Z","timestamp":1756463640000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/jnc.70192"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70192","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2024-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70192"}}