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This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNF\u03b1, INF\u03b3, IL-1\u03b2, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer\u2019s disease could be a consequence of peripheral alteration in the leukocyte inflammation\u2013oxidation state.<\/jats:p>","DOI":"10.3390\/ijms25136976","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"6976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prodromic Inflammatory\u2013Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7028-3083","authenticated-orcid":false,"given":"Noem\u00ed","family":"Cepri\u00e1n","sequence":"first","affiliation":[{"name":"Animal Physiology Unit, Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Investigation Hospital 12 Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Mart\u00ednez de Toda","sequence":"additional","affiliation":[{"name":"Animal Physiology Unit, Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Investigation Hospital 12 Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ianire","family":"Mat\u00e9","sequence":"additional","affiliation":[{"name":"Department of Immunology, Microbiology and Parasitology, Faculty of Pharmacy, University of the Basque Country, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-3330","authenticated-orcid":false,"given":"Antonio","family":"Garrido","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-489X","authenticated-orcid":false,"given":"Lydia","family":"Gimenez-Llort","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Forensic Medicine, Institute of Neuroscience, School of Medicine, Universitat Aut\u00f2noma de Barcelona, Cerdanyola del Vall\u00e8s, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"De la Fuente","sequence":"additional","affiliation":[{"name":"Animal Physiology Unit, Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Institute of Investigation Hospital 12 Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1503\/cmaj.1031789","article-title":"Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: Data from the Canadian Study of Health and Aging","volume":"171","author":"Hsiung","year":"2004","journal-title":"CMAJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jalz.2010.04.006","article-title":"Alzheimer\u2019s disease, a multifactorial disorder seeking multitherapies","volume":"6","author":"Iqbal","year":"2010","journal-title":"Alzheimers Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1001\/jama.2019.9879","article-title":"Association of Lifestyle and Genetic Risk with Incidence of Dementia","volume":"322","author":"Lourida","year":"2019","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. 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