{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:51:07Z","timestamp":1781715067063,"version":"3.54.5"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Physiology &amp; Biophysics, Case Western Reserve University","award":["AG057557"],"award-info":[{"award-number":["AG057557"]}]},{"name":"Department of Physiology &amp; Biophysics, Case Western Reserve University","award":["AG061388"],"award-info":[{"award-number":["AG061388"]}]},{"name":"Department of Physiology &amp; Biophysics, Case Western Reserve University","award":["AG062272"],"award-info":[{"award-number":["AG062272"]}]},{"name":"Department of Physiology &amp; Biophysics, Case Western Reserve University","award":["AG076649"],"award-info":[{"award-number":["AG076649"]}]},{"DOI":"10.13039\/100000002","name":"NIH R01","doi-asserted-by":"publisher","award":["AG057557"],"award-info":[{"award-number":["AG057557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH R01","doi-asserted-by":"publisher","award":["AG061388"],"award-info":[{"award-number":["AG061388"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH R01","doi-asserted-by":"publisher","award":["AG062272"],"award-info":[{"award-number":["AG062272"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH R01","doi-asserted-by":"publisher","award":["AG076649"],"award-info":[{"award-number":["AG076649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes that ultimately lead to dementia. Currently, 50 million people worldwide suffer from dementia related to AD, and the pathogenesis underlying AD pathology and cognitive decline is unknown. While AD is primarily a neurological disease of the brain, individuals with AD often experience intestinal disorders, and gut abnormalities have been implicated as a major risk factor in the development of AD and relevant dementia. However, the mechanisms that mediate gut injury and contribute to the vicious cycle between gut abnormalities and brain injury in AD remain unknown. In the present study, a bioinformatics analysis was performed on the proteomics data of variously aged AD mouse colon tissues. We found that levels of integrin \u03b23 and \u03b2-galactosidase (\u03b2-gal), two markers of cellular senescence, increased with age in the colonic tissue of mice with AD. The advanced artificial intelligence (AI)-based prediction of AD risk also demonstrated the association between integrin \u03b23 and \u03b2-gal and AD phenotypes. Moreover, we showed that elevated integrin \u03b23 levels were accompanied by senescence phenotypes and immune cell accumulation in AD mouse colonic tissue. Further, integrin \u03b23 genetic downregulation abolished upregulated senescence markers and inflammatory responses in colonic epithelial cells in conditions associated with AD. We provide a new understanding of the molecular actions underpinning inflammatory responses during AD and suggest integrin \u03b23 may function as novel target mediating gut abnormalities in this disease.<\/jats:p>","DOI":"10.3390\/ijms24065697","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T03:33:57Z","timestamp":1679024037000},"page":"5697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Integrin \u03b23-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3314-4660","authenticated-orcid":false,"given":"Xin","family":"Tun","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Beachwood High School, Beachwood, OH 44122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Proteomics Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-4795","authenticated-orcid":false,"given":"Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4047-7340","authenticated-orcid":false,"given":"Di","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-neuro-070815-014015","article-title":"Alzheimer\u2019s Disease Mechanisms and Emerging Roads to Novel Therapeutics","volume":"39","year":"2016","journal-title":"Annu. 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