Particulate matter constituents trigger the formation of extracellular amyloid beta and Tau-containing plaques and neurite shortening in vitro

Abstract

IntroductionAir pollution is an environmental factor associated with Alzheimers disease, characterized by decreased cognitive abilities and memory. The limited models of sporadic Alzheimers disease fail to replicate all pathological hallmarks of the disease, making it challenging to uncover potential environmental causes. Environmentally driven models of Alzheimers 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 rate in vitro exposure of neuron-like cells to particulate matter constituents reproduces neurodegenerative phenotype, including extracellular amyloid-{beta} containing plaques and decreased neurite length. ResultsConsistent with the existing in vivo research, 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 rate in vitro model, comprising wild-type neuron-like cells, could serve as an alternative environmentally driven model of Alzheimers disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/586796v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@63faf1org.highwire.dtl.DTLVardef@1eff3cdorg.highwire.dtl.DTLVardef@6f3365org.highwire.dtl.DTLVardef@973a78_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO High dose rate in vitro exposure of neuron-like cells to particulate matter constituents, like diesel exhaust and iron oxide nanoparticles, reproduces neurodegenerative phenotype, including extracellular amyloid--containing plaques and reduction in neurite length and density. C_FIG