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In neurodegenerative disorders, including AD, microglia are often characterized by increased accumulation of lipid droplets (LD), heightened activation, and impaired function. In this study, we examined whether\n                    <jats:italic toggle=\"yes\">Porphyromonas gingivalis<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Pg<\/jats:italic>\n                    ), a keystone periodontal pathogen, promotes LD accumulation in microglia and disrupts their function. We found that infection with\n                    <jats:italic toggle=\"yes\">Pg<\/jats:italic>\n                    (ATCC 33277) induces robust LD accumulation in BV2 microglial cells and in microglia from\n                    <jats:italic toggle=\"yes\">Pg<\/jats:italic>\n                    -infected\n                    <jats:italic toggle=\"yes\">App<\/jats:italic>\n                    knock-in mice. This\n                    <jats:italic toggle=\"yes\">Pg<\/jats:italic>\n                    -driven LD buildup was closely associated with elevated reactive oxygen species (ROS) production, impaired phagocytic ability, and altered activation. Notably, pharmacologic inhibition of LD with a long-chain fatty acyl-CoA synthetase inhibitor effectively reversed\n                    <jats:italic toggle=\"yes\">Pg<\/jats:italic>\n                    -induced LD accumulation, mitigated ROS production, and restored phagocytic function, thus underscoring the critical role of lipid metabolism in regulating microglial function. These findings support a model in which, in the context of periodontitis, systemic dissemination of periodontal pathogens and inflammatory mediators promotes LD accumulation in microglia, and this metabolic alteration exacerbates microglia dysfunction via a self-reinforcing cycle of excessive oxidative stress and impaired phagocytosis, potentially accelerating AD progression.\n                  <\/jats:p>","DOI":"10.1177\/00220345261478558","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:40:36Z","timestamp":1790242836000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Porphyromonas gingivalis<\/i>\n                    Promotes Lipid Droplet\u2013Mediated Microglial Dysfunction"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-4584","authenticated-orcid":false,"given":"M.S.","family":"Riaz Rajoka","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-0122","authenticated-orcid":false,"given":"K.N.","family":"Valladares","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-6063","authenticated-orcid":false,"given":"C.L.","family":"Prairie","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-7464","authenticated-orcid":false,"given":"P.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5403-2281","authenticated-orcid":false,"given":"J.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-2009","authenticated-orcid":false,"given":"S.M.","family":"Michalek","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4585-9893","authenticated-orcid":false,"given":"P.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"crossref","unstructured":"Afzoon S Amiri MA Mohebbi M Hamedani S Farshidfar N. 2023. 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