{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:44:39Z","timestamp":1788385479955,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI20\/00469"],"award-info":[{"award-number":["PI20\/00469"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["4564\/006"],"award-info":[{"award-number":["4564\/006"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["AICO\/2018\/090"],"award-info":[{"award-number":["AICO\/2018\/090"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["CIACIF\/2021\/426"],"award-info":[{"award-number":["CIACIF\/2021\/426"]}]},{"name":"Ayuda a Neurociencias de la Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["PI20\/00469"],"award-info":[{"award-number":["PI20\/00469"]}]},{"name":"Ayuda a Neurociencias de la Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["4564\/006"],"award-info":[{"award-number":["4564\/006"]}]},{"name":"Ayuda a Neurociencias de la Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["AICO\/2018\/090"],"award-info":[{"award-number":["AICO\/2018\/090"]}]},{"name":"Ayuda a Neurociencias de la Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["CIACIF\/2021\/426"],"award-info":[{"award-number":["CIACIF\/2021\/426"]}]},{"name":"FEDER funds, Spain","award":["PI20\/00469"],"award-info":[{"award-number":["PI20\/00469"]}]},{"name":"FEDER funds, Spain","award":["4564\/006"],"award-info":[{"award-number":["4564\/006"]}]},{"name":"FEDER funds, Spain","award":["AICO\/2018\/090"],"award-info":[{"award-number":["AICO\/2018\/090"]}]},{"name":"FEDER funds, Spain","award":["CIACIF\/2021\/426"],"award-info":[{"award-number":["CIACIF\/2021\/426"]}]},{"name":"Direcci\u00f3 General d\u2019Universitat, Investigaci\u00f3 i Ci\u00e8ncia, GVA","award":["PI20\/00469"],"award-info":[{"award-number":["PI20\/00469"]}]},{"name":"Direcci\u00f3 General d\u2019Universitat, Investigaci\u00f3 i Ci\u00e8ncia, GVA","award":["4564\/006"],"award-info":[{"award-number":["4564\/006"]}]},{"name":"Direcci\u00f3 General d\u2019Universitat, Investigaci\u00f3 i Ci\u00e8ncia, GVA","award":["AICO\/2018\/090"],"award-info":[{"award-number":["AICO\/2018\/090"]}]},{"name":"Direcci\u00f3 General d\u2019Universitat, Investigaci\u00f3 i Ci\u00e8ncia, GVA","award":["CIACIF\/2021\/426"],"award-info":[{"award-number":["CIACIF\/2021\/426"]}]},{"name":"GVA-Predoctoral fellowship","award":["PI20\/00469"],"award-info":[{"award-number":["PI20\/00469"]}]},{"name":"GVA-Predoctoral fellowship","award":["4564\/006"],"award-info":[{"award-number":["4564\/006"]}]},{"name":"GVA-Predoctoral fellowship","award":["AICO\/2018\/090"],"award-info":[{"award-number":["AICO\/2018\/090"]}]},{"name":"GVA-Predoctoral fellowship","award":["CIACIF\/2021\/426"],"award-info":[{"award-number":["CIACIF\/2021\/426"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ADAM10 is the main \u03b1-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of \u03b1-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF &lt; 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3\u2032UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.<\/jats:p>","DOI":"10.3390\/ijms24076113","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T03:50:21Z","timestamp":1679629821000},"page":"6113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels"],"prefix":"10.3390","volume":"24","author":[{"given":"Pablo","family":"Ag\u00fcero-Rabes","sequence":"first","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6091-0012","authenticated-orcid":false,"given":"Juli\u00e1n","family":"P\u00e9rez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Secugen S.L., 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-5295","authenticated-orcid":false,"given":"Luc\u00eda","family":"Cremades-Jimeno","sequence":"additional","affiliation":[{"name":"Department of Immunology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz-UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-9752","authenticated-orcid":false,"given":"Mar\u00eda-Salud","family":"Garc\u00eda-Ayll\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-CSIC, 03550 Alicante, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 03550 Alicante, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital General Universitario de Elche, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6227-6040","authenticated-orcid":false,"given":"Adriana","family":"Gea-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-CSIC, 03550 Alicante, Spain"},{"name":"Unidad de Investigaci\u00f3n, Hospital General Universitario de Elche, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Sainz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-6541","authenticated-orcid":false,"given":"Ignacio","family":"Mahillo-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"T\u00e9llez","sequence":"additional","affiliation":[{"name":"Department of Immunology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz-UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0142-9901","authenticated-orcid":false,"given":"Blanca","family":"C\u00e1rdaba","sequence":"additional","affiliation":[{"name":"Department of Immunology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz-UAM, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-320X","authenticated-orcid":false,"given":"Javier","family":"S\u00e1ez-Valero","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Alicante, Universidad Miguel Hern\u00e1ndez-CSIC, 03550 Alicante, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 03550 Alicante, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL), 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-3487","authenticated-orcid":false,"given":"Estrella","family":"G\u00f3mez-Tortosa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a006270","DOI":"10.1101\/cshperspect.a006270","article-title":"Trafficking and Proteolytic Processing of APP","volume":"2","author":"Haass","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1038\/emboj.2010.167","article-title":"ADAM10 is the physiologically relevant, constitutive \u03b1-secretase of the amyloid precursor protein in primary neurons","volume":"29","author":"Kuhn","year":"2010","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101911","DOI":"10.1016\/j.jbc.2022.101911","article-title":"The transmembrane domain of the amyloid precursor protein is required for antiamyloidogenic processing by \u03b1-secretase ADAM10","volume":"298","author":"Hitschler","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Peron, R., Vatanabe, I.P., Manzine, P.R., Camins, A., and Cominetti, M.R. (2018). Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer\u2019s Disease Treatment. Pharmaceuticals, 11.","DOI":"10.3390\/ph11010012"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejphar.2017.06.018","article-title":"Synaptic dysfunction in Alzheimer\u2019s disease: From the role of amyloid \u03b2-peptide to the \u03b1-secretase ADAM10","volume":"817","author":"Musardo","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108661","DOI":"10.1016\/j.biopha.2019.108661","article-title":"ADAM10 in Alzheimer\u2019s disease: Pharmacological modulation by natural compounds and its role as a peripheral marker","volume":"113","author":"Manzine","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1172\/JCI20864","article-title":"A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model","volume":"113","author":"Postina","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s41593-019-0432-1","article-title":"Elevated levels of Secreted-Frizzled-Related-Protein 1 contribute to Alzheimer\u2019s disease pathogenesis","volume":"22","author":"Esteve","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1093\/brain\/awq217","article-title":"Blocking ADAM10 synaptic trafficking generates a model of sporadic Alzheimer\u2019s disease","volume":"133","author":"Epis","year":"2010","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1056507","DOI":"10.3389\/fnagi.2022.1056507","article-title":"The role of ADAM10 in astrocytes: Implications for Alzheimer\u2019s disease","volume":"14","author":"Elsworthy","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.ymthe.2022.03.024","article-title":"The development of ADAM10 endocytosis inhibitors for the treatment of Alzheimer\u2019s disease","volume":"30","author":"Musardo","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF03402076","article-title":"\u03b1-Secretase ADAM10 as well as \u03b1APPs is reduced in platelets and CSF of Alzheimer Disease patients","volume":"8","author":"Colciaghi","year":"2002","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/1354750X.2015.1062554","article-title":"ADAM10 gene expression in the blood cells of Alzheimer\u2019s disease patients and mild cognitive impairment subjects","volume":"20","author":"Manzine","year":"2015","journal-title":"Biomarkers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12974-018-1255-9","article-title":"Levels of ADAM10 are reduced in Alzheimer\u2019s disease CSF","volume":"15","author":"Esteve","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s00406-018-0905-3","article-title":"Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer\u2019s disease patients","volume":"269","author":"Bram","year":"2018","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13195-022-01133-1","article-title":"Proteomic profiling of circulating plasma exosomes reveals novel biomarkers of Alzheimer\u2019s disease","volume":"14","author":"Cai","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3233\/JAD-150737","article-title":"Increase of \u03b1-Secretase ADAM10 in Platelets Along Cognitively Healthy Aging","volume":"50","author":"Schuck","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vatanabe, I.P., Peron, R., Grigoli, M.M., Pelucchi, S., De Cesare, G., Magalh\u00e3es, T., Manzine, P., Balthazar, M.F., Di Luca, M., and Marcello, E. (2021). ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052416"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00018-020-03507-w","article-title":"The metalloproteinase ADAM10 requires its activity to sustain surface expression","volume":"78","author":"Seifert","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1093\/hmg\/ddp323","article-title":"Potential late-onset Alzheimer\u2019s disease-associated mutations in the ADAM10 gene attenuate \u03b1-secretase activity","volume":"18","author":"Kim","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.neuron.2013.08.035","article-title":"ADAM10 Missense Mutations Potentiate \u03b2-Amyloid Accumulation by Impairing Prodomain Chaperone Function","volume":"80","author":"Suh","year":"2013","journal-title":"Neuron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13195-020-00708-0","article-title":"\u03b1-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer\u2019s disease","volume":"12","author":"Sainz","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.brainres.2011.09.008","article-title":"Genetic association between ADAM10 gene polymorphism and Alzheimer\u2019s disease in a Northern Han Chinese population","volume":"1421","author":"Song","year":"2011","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s12640-015-9516-1","article-title":"Genetic Association Between APP, ADAM10 Gene Polymorphism, and Sporadic Alzheimer\u2019s Disease in the Chinese Population","volume":"27","author":"Zeng","year":"2015","journal-title":"Neurotox. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3389\/fgene.2018.00540","article-title":"Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association with Alzheimer\u2019s Disease Risk","volume":"9","author":"Huang","year":"2018","journal-title":"Front. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2229.e1","DOI":"10.1016\/j.neurobiolaging.2012.03.013","article-title":"ADAM10 expression and promoter haplotype in Alzheimer\u2019s disease","volume":"33","author":"Bekris","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neurobiolaging.2010.03.003","article-title":"Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease","volume":"33","author":"Cai","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.neurobiolaging.2009.02.023","article-title":"Lack of evidence to support the association of polymorphisms within the alpha- and beta-secretase genes (ADAM10\/BACE1) with Alzheimer\u2019s disease","volume":"32","author":"Laws","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer\u2019s disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1038\/s41588-022-01208-7","article-title":"Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimer\u2019s Disease","volume":"54","author":"Holstege","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13195-020-00750-y","article-title":"ADAM10 plasma levels predict worsening in cognition of older adults: A 3-year follow-up study","volume":"13","author":"Manzine","year":"2021","journal-title":"Alzheimer Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1212\/01.wnl.0000187068.92184.63","article-title":"Comparison of family histories in FTLD subtypes and related tauopathies","volume":"65","author":"Goldman","year":"2005","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_36","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Anesthesia Analg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer Dement."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:02:01Z","timestamp":1760122921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076113"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076113","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,24]]}}}