Investigation of FadA adhesin from Fusobacterium nucleatum

具核梭杆菌（Fn）是一种革兰氏阴性厌氧菌，是最常见的口腔细菌之一， 与口腔外感染和炎症相关的物种，包括阿尔茨海默病 （AD）。AD患者血清抗Fn抗体水平明显高于正常对照组， 与对照组相比。我们最近发现Fn的FadA粘附素表现出 淀粉样性质。淀粉样蛋白FadA介导宿主细胞的结合和侵袭。 淀粉样蛋白的积累是AD的标志。因此，我们假设淀粉样蛋白- 就像FadA在AD中起作用一样。测试这个假设是我们的亲本R 01的自然延伸， 其研究了淀粉样蛋白样FadA在Fn毒力中的作用，但没有关注AD。因此，在本发明中， 本补充申请是对以下特别利益通知的回应： 针对阿尔茨海默病的NIH赠款的行政补充， 阿尔茨海默病（NOT-AG-20-034）。我们建议检查Fn的存在， AD标本中的淀粉样蛋白样FadA，并与匹配的对照进行比较。淀粉样蛋白的能力- 将在体外和体内检查FadA在诱导AD相关病理中的作用 模型本研究的结果将为AD的病因学和发病机制提供新的线索。

Fusobacterium nucleatum (Fn), a Gram-negative anaerobe, is one of the most prevalent oral species associated with extra-oral infections and inflammation, including Alzheimer’s disease (AD). Serum anti-Fn antibody levels have been found to be significantly higher in AD patients compared to the controls. We have recently discovered that the FadA adhesin of Fn exhibits amyloid-like properties. The amyloid-like FadA mediates binding and invasion of host cells. Accumulation of amyloid proteins is a hallmark of AD. Therefore, we hypothesize that amyloid- like FadA plays a role in AD. Testing this hypothesis is a natural extension of our parent R01, which investigates the role of amyloid-like FadA in Fn virulence, yet not focused on AD. Thus, this supplement application is responsive to the following Notice of Special Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on Alzheimer’s disease (NOT-AG-20-034). We propose to examine the presence of Fn and amyloid-like FadA in AD specimens and compare to matched controls. The ability of amyloid- like FadA in inducing AD-associated pathologies will be examined in both in vitro and in vivo models. Results from this study will shed novel lights on the etiology and mechanism of AD.