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 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. 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 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 and experiments and found that activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. In our experiments, we found that -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 could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which modulates molecular elements in enhancing AD symptoms and signs. Data are available ProteomeXchange with identifier PXD033147.