Detection of the receptor for advanced glycation endproducts in neuronally-derived exosomes in plasma

Biochem Biophys Res Commun. 2018 Jun 12;500(4):892-896. doi: 10.1016/j.bbrc.2018.04.181. Epub 2018 Apr 30.


Exosomes are nanovesicles that participate in cell-to-cell communication and are secreted by a variety of cells including neurons. Recent studies suggest that neuronally-derived exosomes are detectable in plasma and that their contents likely reflect expression of various biomarkers in brain tissues. The receptor for advanced glycation endproducts (RAGE) has been implicated in the pathophysiology of Alzheimer's disease (AD) and is increased in brain regions affected by AD. The goal of our project was to determine whether RAGE is present in plasma exosomes, and specifically exosomes derived from neurons. Exosomes were isolated from plasma samples (n = 8) by precipitation (ExoQuick) and ultracentrifugation methods. Neuronally-derived exosomes were isolated using a biotin-tagged L1 Cell Adhesion Molecule (L1CAM) specific antibody and streptavidin-tagged agarose resin. RAGE expression was measured by Western blots and ELISA. Western Blotting showed that RAGE is present in L1CAM-positive exosomes isolated using both methods. Mean (SD) exosomal RAGE levels were 164 (60) pg/ml by ExoQuick and were highly correlated with plasma sRAGE levels (r = 0.87, p = 0.005), which were approximately 7.5-fold higher than exosomal levels. Weak to moderate correlations were found between exosomal RAGE and age, BMI, and cognitive function. These results show for the first time that RAGE is present in neuronally-derived plasma exosomes, and suggest that exosomal RAGE may be a novel biomarker that reflects pathophysiological processes in the brain.

Keywords: Cognition; Exosomes; Receptor for advanced glycation endproducts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Antigens, Neoplasm / blood
  • Antigens, Neoplasm / genetics*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biotinylation
  • Body Mass Index
  • Brain / metabolism*
  • Brain / pathology
  • Cell Separation / methods
  • Exosomes / chemistry*
  • Exosomes / metabolism
  • Female
  • Gene Expression
  • Humans
  • Male
  • Mitogen-Activated Protein Kinases / blood
  • Mitogen-Activated Protein Kinases / genetics*
  • Neural Cell Adhesion Molecule L1 / chemistry*
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurons / metabolism*
  • Neurons / pathology
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Protein Binding
  • Sepharose / analogs & derivatives
  • Sepharose / chemistry
  • Sepharose / metabolism


  • Antigens, Neoplasm
  • Bacterial Proteins
  • Neural Cell Adhesion Molecule L1
  • streptavidin-agarose
  • Sepharose
  • MOK protein, human
  • Mitogen-Activated Protein Kinases