REPOSITORY > RESULTS

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia, ranking as the 7th deadliest world’s disease. Over 99% of cases are triggered by unknown environmental factors. Despite decades of research, the exact cause remains elusive, and effective treatments are yet to emerge.
Recent epidemiological evidence strongly links cognitive decline to exposure to fine airborne particulate matter (PM2.5), hinting at air pollution's potential role in AD pathogenesis. However, the precise relationship between these particles and neurodegeneration remains elusive.
Employing advanced time-lapse microscopy and analysis, we demonstrate potential mechanism of transport of TiO2 anatase nanotubes from nasal mucosa to the brain after inhalation using a co-culture of immortalized differentiated neuronal SH-SY5Y and microglial HMC3 cell lines. These particles induce structural damage of neurons, triggering key AD hallmarks: amyloid-β (Aβ) plaques, Tau protein aggregation, and neuronal loss. Contrary to common belief, our results suggest the that particles first trigger neuronal structural damage which then translates into pathological changes, with Aβ plaque formation as a consequence. A swift removal of hazardous particles by microglia through phagocytosis reduces axonal damage, neuronal death and results in formation of more compact Aβ plaques, thus mitigating neurodegenerative phenotype observed in monoculture, further strengthening our proposal that neuronal structural damage drives neurodegeneration.
Collectively, we experimentally demonstrate, for the first time, how an environmental factor, like TiO2 nanotubes, could penetrate the brain and instigate a pathological cascade, resembling AD symptoms observed in human patients.