The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer's Pathogenesis via Specific Pathways.
The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer's Pathogenesis via Specific Pathways.
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DOI：
10.3389/fnagi.2022.912709
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病（AD）是老年人最常见的痴呆症，对患者的生活质量产生毁灭性影响，给受影响的个人及其家庭带来重大的社会经济负担。近年来，研究已经确定牙周炎和AD之间的关系。牙周炎是一种感染性/炎症性疾病，破坏牙周支持结构，导致牙齿脱落。口腔微生物组的生态失调在牙周炎的发生和发展中起着重要作用，表现出随着局部炎症的增加，正常微生物群落中的致病菌过度生长的转变。具核梭杆菌是一种常见的病原体，在牙周炎中明显过度生长，也与各种全身性疾病有关。早期的研究报道，F。在AD或认知障碍患者的血清中可以检测到nucleatum，但尚未确定这两种疾病之间的因果关系和合理机制。在本研究中，我们进行了体内和体外实验，发现F。nucleatum激活小胶质细胞，引起小胶质细胞的形态学改变、增殖加速和TNF-α和IL-1β的表达增强。在我们的体内实验中，我们发现F。核酸诱导的牙周炎导致5XFAD小鼠中阿尔茨海默氏症症状的恶化，包括小鼠大脑中认知障碍、β-淀粉样蛋白积累和Tau蛋白磷酸化增加。本研究提示牙周致病菌与AD和F.核质可能是AD发病的危险因素。我们目前正在进一步确定F. nucleatum调节增强AD症状和体征的分子元件。数据可通过ProteomeXchange获得，标识符为PXD 033147。
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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影响因子：
5.4
作者：
Han YW
通讯作者：
Han YW
影响因子：
3.1
作者：
Brook, Itzhak
通讯作者：
Brook, Itzhak
影响因子：
3.2
作者：
Fischer, Jason B.;Prout, Andrew;Warrier, Kavita
通讯作者：
Warrier, Kavita
DOI：
10.1186/s13195-021-00772-0
发表时间：
2021-02-05
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Coomans EM;Schoonhoven DN;Tuncel H;Verfaillie SCJ;Wolters EE;Boellaard R;Ossenkoppele R;den Braber A;Scheper W;Schober P;Sweeney SP;Ryan JM;Schuit RC;Windhorst AD;Barkhof F;Scheltens P;Golla SSV;Hillebrand A;Gouw AA;van Berckel BNM
通讯作者：
van Berckel BNM
影响因子：
14
作者：
Gaugler, Joseph;James, Bryan;Hohman, Timothy J.
通讯作者：
Hohman, Timothy J.