Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

Abstract

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<i>β</i>), the pathogenic peptide associated with Alzheimer's disease (AD), seeded by FapC amyloid fragments (FapCS) of <i>Pseudomonas aeruginosa</i> that colonizes the gut microbiome through infections are examined. FapCS display favorable binding with A<i>β</i> and a catalytic capacity in seeding the peptide amyloidosis. Upon seeding, twisted A<i>β</i> 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<i>β</i> by FapCS and the biofilm fragments derived from <i>P. aeruginosa</i> entail 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<i>β</i> amyloidosis may be exploited as a potential therapeutic target, while the altered mesoscopic signatures of A<i>β</i> fibrils may serve as a prototype for molecular assembly and a biomarker for screening bacterial infections in AD.