{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:10:46Z","timestamp":1790424646240,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    (\n                    <jats:italic>Pg<\/jats:italic>\n                    ), a keystone pathogen in chronic periodontitis, has been identified as an emerging risk factor for Alzheimer\u2019s disease (AD).\n                    <jats:italic>Pg<\/jats:italic>\n                    can promote the accumulation of amyloid \u03b2 protein (A\u03b2), a characteristic feature of AD pathology. However, the underlying mechanism, particularly in A\u03b2 clearance, remains poorly understood. Here, by using 3 different strains of\n                    <jats:italic>Pg<\/jats:italic>\n                    , ATCC33277, W50, and W83, we discovered that APP\/PS1 mice infected with all 3\n                    <jats:italic>Pg<\/jats:italic>\n                    strains showed decreased microglial A\u03b2 internalization, increased A\u03b2 deposition in the brain, and impaired cognitive function. Using in vitro experiments, we further demonstrated that all 3\n                    <jats:italic>Pg<\/jats:italic>\n                    strains inhibited microglial A\u03b2 clearance, where gingipains, a group of toxic proteases derived from\n                    <jats:italic>Pg<\/jats:italic>\n                    , were involved. Gingipains were shown to hydrolyze CD14, subsequently impeding the CD14-mediated Vav-Rac\/Cdc42 signaling cascade, which ultimately suppressed phagocytosis. Gingipain inhibitor could effectively restore microglial A\u03b2 clearance and diminish A\u03b2 deposition, leading to improved cognitive function in\n                    <jats:italic>Pg<\/jats:italic>\n                    -infected APP\/PS1 mice. These findings may provide new insights into the mechanism through which\n                    <jats:italic>Pg<\/jats:italic>\n                    impairs microglial A\u03b2 clearance to aggravate AD phenotypes, suggesting that gingipain inhibitors could be potential therapeutics for treating\n                    <jats:italic>Pg<\/jats:italic>\n                    -associated AD.\n                  <\/jats:p>","DOI":"10.1177\/00220345241294009","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:43:16Z","timestamp":1739580196000},"page":"408-418","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>Porphyromonas gingivalis<\/i>\n                    Impairs Microglial A\u03b2 Clearance in a Mouse Model"],"prefix":"10.1177","volume":"104","author":[{"given":"M.","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and 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