Targeting Both Monomer and Oligomer with Fibrinogen Efficiently Suppresses Amyloid Fibril Formation and Cell Toxicity of Amyloid β 1-42.

The development of drugs for Alzheimer's disease, which accounts for over half of all dementia cases, remains challenging. Amyloid β 1-42 (Aβ42) is widely recognized for its deposition in the brains of patients with Alzheimer's disease. Furthermore, Aβ42-induced cell toxicity likely plays a role in disease onset. Molecular species present in the early stages, such as monomers and oligomers, are appropriate therapeutic targets for suppressing amyloid fibril formation and cell toxicity. In this study, we investigated the effects of bovine fibrinogen (bFg) and human fibrinogen (hFg) since these molecules have been known to exhibit chaperone-like activities. Our findings indicate that bFg exerts a strong inhibitory effect on amyloid fibril formation. Dot blot assays, analytical ultracentrifugation (AUC), and atomic force microscopy (AFM) suggest that bFg interacts with both Aβ42 monomers and oligomers. In contrast, human fibrinogen (hFg), which interacts only with oligomers, exhibits a weaker inhibitory effect on amyloid fibril formation. Moreover, bFg significantly rescued cells from Aβ42-induced toxicity, whereas hFg provided only partial protection. These findings underscore the potential of molecules targeting early stage Aβ42 species as promising candidates for Alzheimer's disease treatment.