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The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways

Alzheimer’s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient’s 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 betwe...

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Autores principales: Wu, Hongle, Qiu, Wei, Zhu, Xiaofang, Li, Xiangfen, Xie, Zhongcong, Carreras, Isabel, Dedeoglu, Alpaslan, Van Dyke, Thomas, Han, Yiping W., Karimbux, Nadeem, Tu, Qisheng, Cheng, Lei, Chen, Jake
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260256/
https://www.ncbi.nlm.nih.gov/pubmed/35813949
http://dx.doi.org/10.3389/fnagi.2022.912709
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author Wu, Hongle
Qiu, Wei
Zhu, Xiaofang
Li, Xiangfen
Xie, Zhongcong
Carreras, Isabel
Dedeoglu, Alpaslan
Van Dyke, Thomas
Han, Yiping W.
Karimbux, Nadeem
Tu, Qisheng
Cheng, Lei
Chen, Jake
author_facet Wu, Hongle
Qiu, Wei
Zhu, Xiaofang
Li, Xiangfen
Xie, Zhongcong
Carreras, Isabel
Dedeoglu, Alpaslan
Van Dyke, Thomas
Han, Yiping W.
Karimbux, Nadeem
Tu, Qisheng
Cheng, Lei
Chen, Jake
author_sort Wu, Hongle
collection PubMed
description Alzheimer’s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient’s 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. Fusobacterium nucleatum 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 F. nucleatum 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 in vivo and in vitro experiments and found that F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. In our in vivo experiments, we found that F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s 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 F. nucleatum could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which F. nucleatum modulates molecular elements in enhancing AD symptoms and signs. Data are available via ProteomeXchange with identifier PXD033147.
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spelling pubmed-92602562022-07-08 The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways Wu, Hongle Qiu, Wei Zhu, Xiaofang Li, Xiangfen Xie, Zhongcong Carreras, Isabel Dedeoglu, Alpaslan Van Dyke, Thomas Han, Yiping W. Karimbux, Nadeem Tu, Qisheng Cheng, Lei Chen, Jake Front Aging Neurosci Neuroscience Alzheimer’s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient’s 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. Fusobacterium nucleatum 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 F. nucleatum 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 in vivo and in vitro experiments and found that F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. In our in vivo experiments, we found that F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s 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 F. nucleatum could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which F. nucleatum modulates molecular elements in enhancing AD symptoms and signs. Data are available via ProteomeXchange with identifier PXD033147. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9260256/ /pubmed/35813949 http://dx.doi.org/10.3389/fnagi.2022.912709 Text en Copyright © 2022 Wu, Qiu, Zhu, Li, Xie, Carreras, Dedeoglu, Van Dyke, Han, Karimbux, Tu, Cheng and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wu, Hongle
Qiu, Wei
Zhu, Xiaofang
Li, Xiangfen
Xie, Zhongcong
Carreras, Isabel
Dedeoglu, Alpaslan
Van Dyke, Thomas
Han, Yiping W.
Karimbux, Nadeem
Tu, Qisheng
Cheng, Lei
Chen, Jake
The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title_full The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title_fullStr The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title_full_unstemmed The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title_short The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
title_sort periodontal pathogen fusobacterium nucleatum exacerbates alzheimer’s pathogenesis via specific pathways
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260256/
https://www.ncbi.nlm.nih.gov/pubmed/35813949
http://dx.doi.org/10.3389/fnagi.2022.912709
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