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One emerging hypothesis is organ involvement in the process of A\u03b2 clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red\/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms25116112","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T08:19:42Z","timestamp":1717402782000},"page":"6112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer\u2019s Disease and Its Exacerbation with Sex and Social Isolation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-4360","authenticated-orcid":false,"given":"Juan","family":"Fraile-Ramos","sequence":"first","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Reig-Vilallonga","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-489X","authenticated-orcid":false,"given":"Lydia","family":"Gim\u00e9nez-Llort","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/138161210793176572","article-title":"Neuroinflammation, Oxidative Stress and the Pathogenesis of Alzheimer\u2019s Disease","volume":"16","author":"Agostinho","year":"2010","journal-title":"Curr. 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