In situ fibrillizing amyloid-beta 1-42 induces neurite degeneration and apoptosis of differentiated SH-SY5Y cells

PLoS One. 2017 Oct 24;12(10):e0186636. doi: 10.1371/journal.pone.0186636. eCollection 2017.


The progression of Alzheimer's disease is causatively linked to the accumulation of amyloid-β aggregates in the brain, however, it is not clear how the amyloid aggregates initiate the death of neuronal cells. The in vitro toxic effects of amyloid peptides are most commonly examined using the human neuroblastoma derived SH-SY5Y cell line and here we show that differentiated neuron-like SH-SY5Y cells are more sensitive to amyloid peptides than non-differentiated cells, because the latter lack long neurites. Exogenous soluble amyloid-β 1-42 covered cell bodies and whole neurites in differentiated cells with dense fibrils, causing neurite beading and fragmentation, whereas preformed amyloid-β 1-42 fibrils had no toxic effects. Importantly, spontaneously fibrillizing amyloid-β 1-42 peptide exhibited substantially higher cellular toxicity than amyloid-β 1-40, which did not form fibrils under the experimental conditions. These results support the hypothesis that peptide toxicity is related to the active fibrillization process in the incubation mixture.

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Apoptosis*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Differentiation*
  • Cell Line, Tumor
  • Humans
  • Neurites*
  • Peptide Fragments / metabolism*


  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Peptide Fragments
  • amyloid beta-protein (1-42)

Grant support

This work was supported by the Estonian Research Council (grant IUT 19-8) to PP and Estonian Science Foundation grant 9318 to VT.