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Particulate Matter Constituents Trigger the Formation of Extracellular Amyloid β and Tau-containing Plaques and Neurite Shortening In Vitro

14 November 2024

Abstract
Air pollution is an environmental factor associated with an increased risk of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, 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. We used live-cell confocal fluorescent imaging combined with high-resolution stimulated emission depletion (STED) microscopy to follow the response of retinoic acid-differentiated human neuroblastoma SH-SY5Y cells to nanomaterial exposure. Here, we report that exposure of the cells to some particulate matter constituents reproduces a neurodegenerative phenotype, including extracellular amyloid beta-containing plaques and decreased neurite length. Consistent 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. Although the exact mechanism behind this effect remains to be explained, the retinoic acid differentiated SH-SY5Y cell in vitro model could serve as an alternative, environmentally driven model of neurodegenerative diseases, including Alzheimer’s disease.

About the Authors

This study is a collaborative effort involving nanoPASS partners from multiple prestigious institutions:

  • Aleksandar Sebastijanović, Iztok Urbančič, and Tilen Koklič from the Laboratory of Biophysics, Jožef Stefan Institute, Slovenia
  • Laura Maria Azzurra Camassa and Shan Zienolddiny-Narui from the National Institute of Occupational Health, Norway
  • Vilhelm Malmborg and Joakim Pagels from Lund University, Sweden
  • Slavko Kralj from the Jožef Stefan Institute, Slovenia
  • Janez Štrancar from Infinite LLC, Slovenia
  • Ulla Vogel from the National Research Centre for the Working Environment, Denmark

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