Helicobacter Pylori Outer Membrane Vesicles Directly Promote Aβ Aggregation and Enhance Aβ Toxicity in APP/PS1 Mice

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Nov 8

PMID 39516239

Authors

Dongli Meng

Yiwen Lai

Lun Zhang

Wenting Hu

Hui Wei

Cuiping Guo

Xiaopeng Jing

Huan Zhou

Rui Xiao

Liping Zhu

Shengquan Luo

Zhendong Xu

Yu Chen

Xiaochuan Wang

Rong Liu

Ji Zeng

Affiliations

Soon will be listed here.

Abstract

Helicobacter pylori (H. pylori) infection has been found associated with Alzheimer's disease (AD) with unclear mechanisms. Outer Membrane Vesicles (OMVs) are spherical particles secreted by Gram-negative bacteria. Here we explore the effect of H. pylori OMVs on Aβ aggregation and toxicity. We show intraperitoneally-injected H. pylori OMVs enter the brain and co-localize with Aβ plaques in APP/PS1 mice, accompanied by aggravated Aβ pathology, exacerbated cognitive deficits and synaptic impairment, indicating that H. pylori OMVs promote β-amyloidosis and AD development. The in vitro results further identify that H. pylori OMVs significantly accelerate Aβ aggregation and increase Aβ-induced neurotoxicity. Through lipidomic analysis, we reveal that lipid components, particularly LPC 18:0 in H. pylori OMVs accelerate Aβ aggregation and enhance Aβ neurotoxicity. Moreover, H. pylori OMVs-enhanced Aβ neurotoxicity is mediated by Ca. These findings reveal a mechanism of H. pylori OMVs in accelerating AD development in which the bacterial OMVs-originated lipid components play a key role in promoting Aβ aggregation and neurotoxicity.

Citing Articles

Polymicrobial interactions of and its role in the process of oral diseases.

Fan Y, Chen X, Shan T, Wang N, Han Q, Ren B J Oral Microbiol. 2025; 17(1):2469896.

PMID: 40013013 PMC: 11864007. DOI: 10.1080/20002297.2025.2469896.

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