Membrane Trafficking Pathways in Alzheimer's Disease

Authors

  • Lawrence Rajendran,

    Corresponding author
    • Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Wim Annaert

    Corresponding author
    1. Laboratory for Membrane Trafficking, Center for Human Genetics (KULeuven) & VIB-Center for the Biology of Disease, Leuven, Belgium
    • Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
    Search for more papers by this author

Corresponding authors: Lawrence Rajendran, rajendran@bli.uzh.ch and Wim Annaert, Wim.Annaert@cme.vib-kuleuven.be

Abstract

Membrane proteins are constantly being trafficked in cells and the relevant proteins in Alzheimer's disease (AD), such as the amyloid precursor protein (APP) and its processing enzymes, are not exempted from that. Molecular cell biologists have been endeavoring to ascertain a roadmap for APP processing and trafficking in various cell types including neurons. This has led to the identification of numerous regulatory sorting mechanisms, protein–protein interactions and lipidic microenvironments that largely define how and where the substrate APP meets its processing enzymes. However, the cell biology of tau, and the formation of neurofibrillary tangles, has long been regarded as a separate field. Nonetheless, recent progress is bringing both worlds together in a new paradigm on how Aβ toxicity and tau are physiologically connected. Here, we discuss an update of our current appraisal on how membrane trafficking may play an important role in the pathogenesis of the disease and how this could be exploited for effective therapy.

image

Ancillary