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Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Helicobacter pylori outer membrane vesicles directly promote Aβ aggregation and enhance Aβ toxicity in APP/PS1 mice
Dongli Meng1,2, Yiwen Lai1, Lun Zhang1,3
1Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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 Ca2+. 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.
Insights
Helicobacter pylori outer membrane vesicles accelerate Alzheimer's disease (AD) pathology by promoting amyloid-beta aggregation and neurotoxicity. Specific lipids within these bacterial vesicles, like LPC 18:0, are key drivers of this harmful process.
Area of Science:
- Neuroscience
- Microbiology
- Biochemistry
Background:
- Helicobacter pylori (H. pylori) infection is linked to Alzheimer's disease (AD), but the underlying mechanisms remain unclear.
- Outer Membrane Vesicles (OMVs) are bacterial components that may play a role in disease pathogenesis.
Purpose of the Study:
- To investigate the impact of H. pylori OMVs on amyloid-beta (Aβ) aggregation and neurotoxicity.
- To elucidate the role of H. pylori OMVs in the development and progression of AD.
Main Methods:
- Administration of H. pylori OMVs to APP/PS1 transgenic mice.
- In vitro assays to assess Aβ aggregation and neurotoxicity.
- Lipidomic analysis of H. pylori OMVs.
- Calcium ion (Ca2+) measurements.
Main Results:
- H. pylori OMVs entered the brain, co-localized with Aβ plaques, and worsened AD pathology and cognitive deficits in mice.
- In vitro, H. pylori OMVs significantly accelerated Aβ aggregation and increased Aβ-induced neurotoxicity.
- Lipid components, notably LPC 18:0, within H. pylori OMVs were identified as key factors promoting Aβ aggregation and neurotoxicity.
- H. pylori OMVs-mediated neurotoxicity involved calcium ion (Ca2+) signaling.
Conclusions:
- H. pylori OMVs promote β-amyloidosis and AD development.
- Bacterial OMVs, particularly their lipid components, contribute to Aβ aggregation and neurotoxicity, offering a potential mechanism linking H. pylori infection to AD.
