Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

TY - JOUR

T1 - Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

AU - Javed, Ibrahim

AU - Zhang, Zhenzhen

AU - Adamcik, Jozef

AU - Andrikopoulos, Nicholas

AU - Li, Yuhuan

AU - Otzen, Daniel E.

AU - Lin, Sijie

AU - Mezzenga, Raffaele

AU - Davis, Thomas P.

AU - Ding, Feng

AU - Ke, Pu Chun

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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 (Aβ), the pathogenic peptide associated with Alzheimer's disease (AD), seeded by FapC amyloid fragments (FapCS) of Pseudomonas aeruginosa that colonizes the gut microbiome through infections are examined. FapCS display favorable binding with Aβ and a catalytic capacity in seeding the peptide amyloidosis. Upon seeding, twisted Aβ 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 Aβ by FapCS and the biofilm fragments derived from P. aeruginosa 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 Aβ amyloidosis may be exploited as a potential therapeutic target, while the altered mesoscopic signatures of Aβ fibrils may serve as a prototype for molecular assembly and a biomarker for screening bacterial infections in AD.

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

KW - amyloid diseases

KW - amyloidosis

KW - brain health cross seeding

KW - gut–brain axis

KW - neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=85088116453&partnerID=8YFLogxK

U2 - 10.1002/advs.202001299

DO - 10.1002/advs.202001299

M3 - Journal article

C2 - 32999841

AN - SCOPUS:85088116453

SN - 2198-3844

VL - 7

JO - Advanced Science

JF - Advanced Science

IS - 18

M1 - 2001299

ER -