{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:01:19Z","timestamp":1789624879620,"version":"build-2803163510"},"reference-count":47,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260241"],"award-info":[{"award-number":["82260241"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Science-brain Basic Research Foundation","award":["SL2023A04J02219"],"award-info":[{"award-number":["SL2023A04J02219"]}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2015GXNSFAA139171 and 2020GXNSFAA259053"],"award-info":[{"award-number":["2015GXNSFAA139171 and 2020GXNSFAA259053"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangxi Medical and Health Appropriate Technology Development and Application Project","award":["S2022091"],"award-info":[{"award-number":["S2022091"]}]},{"name":"Guangxi Key Research and Development Project","award":["AB24010094"],"award-info":[{"award-number":["AB24010094"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periodontal disease has two types of inflammatory states: gingivitis and periodontitis. While studies suggest a link between periodontal disease and Alzheimer's disease (AD), current evidence is insufficient to establish causality. This study employed Mendelian randomization (MR) and bioinformatics to investigate causal relationships between gingivitis, periodontitis, and AD types, while identifying diagnostic biomarkers through transcriptome-based bioinformatics approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to explore the causal relationship between periodontal disease and AD using MR combined with bioinformatics analysis, investigate potential pathogenesis, and construct\/validate diagnostic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Exposures and outcomes were selected from the Open whole-genome association study. Causal relationships were assessed using inverse variance-weighted (IVW), MR-Egger, and other supplementary methods. Transcriptome sequencing datasets were downloaded from Gene Expression Omnibus datasets. Key pathways and functions were identified through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Protein-protein interaction and LASSO regression were used to construct and evaluate the diagnostic signature for early-onset AD (EOAD). Gene Set Enrichment Analysis was applied to analyze gene set enrichment between high and low-risk groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IVW showed a positive correlation (OR\u2009=\u20091.161, 95% CI\u2009=\u20091.011\u20131.332, p\u2009=\u20090.035), and MR-Egger validated this result (OR\u2009=\u20091.296, 95% CI\u2009=\u20091.020\u20131.645, p\u2009=\u20090.049). These findings suggest that chronic gingivitis may increase EOAD risk. Reverse analysis results were negative. Immune activation, angiogenesis, and blood-brain barrier damage link the two diseases. The Inter-alpha-trypsin inhibitor heavy chain H5 (\n                      <jats:italic>ITIH5<\/jats:italic>\n                      ) gene and\n                      <jats:italic>TGFB<\/jats:italic>\n                      pathway emerged in MR and bioinformatics analyses. A gene signature composed of\n                      <jats:italic>ITIH5<\/jats:italic>\n                      ,\n                      <jats:italic>MFAP4<\/jats:italic>\n                      , and\n                      <jats:italic>PRELP<\/jats:italic>\n                      shows potential for diagnosing EOAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Chronic gingivitis may be associated with an increased risk of EOAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251336259","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T02:28:56Z","timestamp":1746412136000},"page":"1321-1340","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic gingivitis increases the risk of early-onset Alzheimer's disease"],"prefix":"10.1177","volume":"105","author":[{"given":"Dongcan","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozuo","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9262-4639","authenticated-orcid":false,"given":"Pingkai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoju","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-5567","authenticated-orcid":false,"given":"LiuYu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-2143","authenticated-orcid":false,"given":"Li","family":"Chi","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Stomatology, Hospital of Stomatology, Institute of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0543-9763","authenticated-orcid":false,"given":"Man","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.87"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000687"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160314150501"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316201"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.4103\/0028-3886.173623"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.570992"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/137357"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210465"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3034"},{"key":"e_1_3_5_12_2","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies NM","year":"2018","unstructured":"Davies NM, Holmes MV, Davey Smith G. 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