Particulate matter constituents trigger the formation of extracellular amyloid β and Tau-containing plaques and neurite shorteningin vitro

Abstract

AbstractIntroductionAir pollution is an environmental factor associated with Alzheimer’s disease, characterized by decreased cognitive abilities and memory. The limited models of sporadic Alzheimer’s disease fail to replicate all pathological hallmarks of the disease, making it challenging to uncover potential environmental causes. Environmentally driven models of Alzheimer’s disease are thus timely and necessary.MethodsWe used live-cell confocal fluorescent imaging combined with high-resolution stimulated emission depletion (STED) microscopy to follow the response of neuron-like cells to nanomaterial exposure. Here, we report that a high dose ratein vitroexposure of neuron-like cells to particulate matter constituents reproduces neurodegenerative phenotype, including extracellular amyloid-β containing plaques and decreased neurite length.ResultsConsistent with the existingin vivoresearch, we observed detrimental effects, specifically a substantial reduction in neurite length and formation of amyloid beta plaques, after exposure to iron oxide and diesel exhaust particles. Conversely, after exposure to engineered cerium oxide nanoparticles, the lengths of neurites were maintained, and almost no extracellular amyloid beta plaques were formed.DiscussionAlthough the exact mechanism behind this effect remains to be explained, the high dose ratein vitromodel, comprising wild-type neuron-like cells, could serve as an alternative environmentally driven model of Alzheimer’s disease.Abstract FigureGraphical abstractHigh dose ratein vitroexposure of neuron-like cells to particulate matter constituents, like diesel exhaust and iron oxide nanoparticles, reproduces neurodegenerative phenotype, including extracellular amyloid-β-containing plaques and reduction in neurite length and density.