Neurodegenerative effects of air pollutant Particles: Biological mechanisms implicated for Early-Onset Alzheimer's disease.

BACKGROUND

Sporadic Alzheimer's disease (AD) occurs in 99% of all cases and can be influenced by air pollution such as diesel emissions and more recently, an iron oxide particle, magnetite, detected in the brains of AD patients. However, a mechanistic link between air pollutants and AD development remains elusive.

AIM: To study the development of AD-relevant pathological effects induced by air pollutant particle exposures and their mechanistic links, in wild-type and AD-predisposed models.

METHODS

C57BL/6 (n = 37) and APP/PS1 transgenic (n = 38) mice (age 13 weeks) were exposed to model pollutant iron-based particle (Fe0-Fe3O4, dTEM = 493 ± 133 nm), hydrocarbon-based diesel combustion particle (43 ± 9 nm) and magnetite (Fe3O4, 153 ± 43 nm) particles (66 µg/20 µL/third day) for 4 months, and were assessed for behavioural changes, neuronal cell loss, amyloid-beta (Aβ) plaque, immune response and oxidative stress-biomarkers. Neuroblastoma SHSY5Y (differentiated) cells were exposed to the particles (100 μg/ml) for 24 h, with assessments on immune response biomarkers and reactive oxygen species generation.

RESULTS

Pollutant particle-exposure led to increased anxiety and stress levels in wild-type mice and short-term memory impairment in AD-prone mice. Neuronal cell loss was shown in the hippocampal and somatosensory cortex, with increased detection of Aβ plaque, the latter only in the AD-predisposed mice, with the wild-type not genetically disposed to form the plaque. The particle exposures however, increased AD-relevant immune system responses, including inflammation, in both strains of mice. Exposures also stimulated oxidative stress, although only observed in wild-type mice. The in vitro studies complemented the immune response and oxidative stress observations.

CONCLUSIONS

This study provides insights into the mechanistic links between inflammation and oxidative stress to pollutant particle-induced AD pathologies, with magnetite apparently inducing the most pathological effects. No exacerbation of the effects was observed in the AD-predisposed model when compared to the wild-type, indicating a particle-induced neurodegeneration that is independent of disease state.