Investigation of FadA adhesin from Fusobacterium nucleatum

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.