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Aging Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient\u2019s quality of life, which creates a significant socio-economic burden for the affected individuals and their families. In recent years, studies have identified a relationship between periodontitis and AD. Periodontitis is an infectious\/inflammatory disease that destroys the supporting periodontal structure leading to tooth loss. Dysbiosis of the oral microbiome plays a significant role in the onset and development of periodontitis exhibiting a shift to overgrowth of pathobionts in the normal microflora with increasing local inflammation.\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    is a common pathogen that significantly overgrows in periodontitis and has also been linked to various systemic diseases. Earlier studies have reported that antibodies to\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    can be detected in the serum of patients with AD or cognitive impairment, but a causal relationship and a plausible mechanism linking the two diseases have not been identified. In this study, we conducted both\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments and found that\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-\u03b1 and IL-1\u03b2 in microglial cells. In our\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments, we found that\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    -induced periodontitis resulted in the exacerbation of Alzheimer\u2019s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. This study may suggest a possible link between a periodontal pathogen and AD and\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    modulates molecular elements in enhancing AD symptoms and signs. Data are available\n                    <jats:italic>via<\/jats:italic>\n                    ProteomeXchange with identifier PXD033147.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2022.912709","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T04:21:32Z","timestamp":1655958092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":66,"title":["The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer\u2019s Pathogenesis via Specific Pathways"],"prefix":"10.3389","volume":"14","author":[{"given":"Hongle","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongcong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Carreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpaslan","family":"Dedeoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping W.","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Karimbux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"B1","year":"2020","journal-title":"Alzheimer\u2019s and Dementia: the Journal of the Alzheimer\u2019s Association."},{"key":"B2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4103\/1947-2714.159325","article-title":"Association between periodontitis and Alzheimer\u2019s Disease.","volume":"7","author":"Abbayya","year":"2015","journal-title":"N. 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