Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

The gut-brain axis has attracted increasing attention in recent years, fueled by accumulating symptomatic, physiological, and pathological findings. In this study, the aggregation and toxicity of amyloid beta (A beta), the pathogenic peptide associated with Alzheimer's disease (AD), seeded by FapC amyloid fragments (FapCS) ofPseudomonas aeruginosathat colonizes the gut microbiome through infections are examined. FapCS display favorable binding with A beta and a catalytic capacity in seeding the peptide amyloidosis. Upon seeding, twisted A beta fibrils assume a much-shortened periodicity approximating that of FapC fibrils, accompanied by a 37% sharp rise in the fibrillar diameter, compared with the control. The robust seeding capacity for A beta by FapCS and the biofilm fragments derived fromP. aeruginosaentail abnormal behavior pathology and immunohistology, as well as impaired cognitive function of zebrafish. Together, the data offer the first concrete evidence of structural integration and inheritance in peptide cross-seeding, a crucial knowledge gap in understanding the pathological correlations between different amyloid diseases. The catalytic role of infectious bacteria in promoting A beta amyloidosis may be exploited as a potential therapeutic target, while the altered mesoscopic signatures of A beta fibrils may serve as a prototype for molecular assembly and a biomarker for screening bacterial infections in AD.