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

Frontiers in Aging Neuroscience

Nadeem Karimbux¹  Alpaslan Dedeoglu³  Thomas Van Dyke⁵  Yiping W. Han⁷  Isabel Carreras⁹  Jake Chen^1,10  Xiaofang Zhu^1,10  Qisheng Tu^1,10  Wei Qiu^1,11  Hongle Wu^1,13  Lei Cheng^1,13  Zhongcong Xie^1,14  Xiangfen Li^1,15 

[1] Immunology, Vagelos College of Physicians &Surgeons, Columbia University Irvign Medical Center, New York, NY, United States;0Department of Neurology School of Medicine, Boston University, Boston, MA, United States;1The Forsyth Institute, Clinical and Translational Research, Cambridge, MA, United States;2Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States;3Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, University Irvign Medical Center, New York, NY, United States;;4Department of Microbiology &Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China;Department of Neurology and Department of Biochemistry School of Medicine, Boston University, Boston, MA, United States;Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA, United States;Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China;Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, United States;Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, United States;Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States;State Key Laboratory of Oral Disease, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China;

关键词: F. nucleatum;    inflammation;    periodontitis;    Alzheimer’s Disease;    mouse model;   

DOI  :  10.3389/fnagi.2022.912709

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown