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Accumulation of the amyloid-beta precursor protein in multivesicular body-like organelles

Marcel M Verbeek1, Irene Otte-Höller, Jack A M Fransen

  • 1Department of Neurology, University Medical Center Nijmegen, The Netherlands. m.verbeek@ckslkn.azn.nl

The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
|April 23, 2002
PubMed

Insights

Interferon-gamma and chloroquine cause amyloid precursor protein (APP) to accumulate in cellular organelles, reducing its secretion. These findings highlight the role of multivesicular bodies in APP trafficking and processing.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Protein Biochemistry

Background:

  • Amyloid-beta protein production involves proteolytic cleavage of its precursor (APP).
  • The intracellular location of APP processing is not fully understood.
  • APP processing may occur in different cellular compartments.

Purpose of the Study:

  • To investigate the effect of modulating amyloid precursor protein (APP) localization on its processing.
  • To identify the intracellular organelles involved in APP trafficking and amyloid-beta production.

Main Methods:

  • Cultured human leptomeningeal smooth muscle cells and brain pericytes were used.
  • Immunofluorescence and immunoelectron microscopy were employed to track APP localization.
  • Interferon-gamma, chloroquine, IL-1, IL-6, and TNF-alpha were used to modulate APP processing.

Main Results:

  • APP was found in intracellular vesicles, including lysosomes, under normal conditions.
  • Interferon-gamma and chloroquine induced APP accumulation in multivesicular body-like organelles.
  • These organelles were identified as part of the endocytic pathway.
  • APP secretion was reduced by interferon-gamma or chloroquine.

Conclusions:

  • Multivesicular body-like organelles serve as intermediate compartments for APP intracellular trafficking.
  • APP accumulation in these organelles correlates with reduced secretion.
  • This suggests a role for endocytic pathway organelles in regulating amyloid-beta precursor protein processing.

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