The release and transmission of amyloid precursor protein via exosomes

Neurochem Int. 2018 Mar:114:18-25. doi: 10.1016/j.neuint.2017.12.009. Epub 2017 Dec 23.

Abstract

Amyloid precursor protein (APP) processing is central in Alzheimer's disease (AD) pathogenesis. The healthy unaffected neurons suffer the transmission of amyloid protein from pathologically affected neurons, which may play an important role in the anatomical spread of the disease. Exosomes are appropriate candidates for transmission of amyloid species, because of their potential role as "intercellular transportation". To address a role of secreted exosomes in neuronal homeostasis in AD, we harvested exosomes from the conditioned medium of HEK293-APP Swe/Ind cells. We have demonstrated that these exosomes contained APP and were capable of efficiently transferring APP to normal primary neurons. Moreover, these exosomes had dose-dependent detrimental effect on cultured neurons. Our results suggest a key mechanism underlying the spread of amyloid protein in the brain and the acceleration of pathology in AD; exosomes secretion serves to amplify and propagate Alzheimer's disease related pathology.

Keywords: APP; Exosomes; HEK293-APPSwe/Ind cells; Neurotoxicity; Transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / administration & dosage
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Exosomes / metabolism*
  • HEK293 Cells
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism*
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Amyloid beta-Protein Precursor