Indoor aerosols induced blood-brain barrier leakiness and β-amyloid1-42 aggregation.

INTRODUCTION

Exposure to indoor aerosols that include fine particulate matter 2.5 (PM2.5) and microorganisms has been implicated in various health issues, including neurodegenerative diseases.

OBJECTIVES

The major components of indoor aerosols could induce the blood-brain barrier (BBB) leakiness and β amyloid (Aβ) aggregation, potentially exacerbating Alzheimer's disease (AD) pathology.

METHODS

The main components of aerosols were collected by an intelligent sampler and an airborne microorganism sampler, respectively. The PM2.5 was characterized with SEM and UV-vis spectrophotometer. The microorganisms were identified by 16S rRNA gene sequencing. The Aβ aggregation was studied by thioflavin T kinetic assay and circular dichroism spectroscopy. The BBB models were constructed by seeding astrocytes and human brain microvascular endothelial cells on the membrane of transwell inserts. Moreover, the BBB leakiness induced by PM2.5, Staphylococcus aureus (S. aureus), and the Aβ aggregates was evaluated by immunofluorescence imaging and transwell assay both in vitro and in vivo.

RESULTS

The PM2.5 owns the size of 112 ± 35.41 nm and the surface charge of -0.125 mV. PM2.5 and S. aureus can independently disrupt the BBB integrity both in vitro and in vivo by down-regulating adherens and tight junction proteins including zonula occludens-1, VE-cadherin, occludin, and claudin-5. Furthermore, PM2.5 and S. aureus accelerated Aβ aggregation into neurotoxic oligomers and fibrils. In combined exposures, PM2.5 + Aβ or S. aureus + Aβ act synergistically to exacerbate BBB permeability and cytotoxicity of endothelial cells, astrocytes, and neuron cells, creating a vicious cycle of the BBB dysfunction and neurodegeneration.

CONCLUSIONS

These findings establish PM2.5 and S. aureus as dual environmental drivers of BBB compromise and Aβ pathology, offering novel mechanistic insights and emphasizing the urgent need for strategies to mitigate indoor aerosol-related health risks for AD patients.