The physical approximation of APP and BACE-1: A key event in alzheimer's disease pathogenesis

Dev Neurobiol. 2018 Mar;78(3):340-347. doi: 10.1002/dneu.22556. Epub 2017 Nov 13.


Alzheimer's disease (AD) is characterized by the accumulation of insoluble deposits of Amyloid β (Aβ) in brains. Aβ is derived by sequential cleavage of the amyloid precursor protein (APP) by β-site secretase enzyme (BACE-1) and γ-secretase. Proteolytic processing of APP by BACE-1 is the rate-limiting step in Aβ production, and this pathway is a prime target for AD drug development. Both APP and BACE-1 are membrane-spanning proteins, transported via secretory and endocytic pathways; and the physical interaction of APP and BACE-1 during trafficking is a key cell biological event initiating the amyloidogenic pathway. Here, we highlight recent research on intracellular trafficking/sorting of APP and BACE-1, and discuss how dysregulation of these pathways might lead to enhanced convergence of APP and BACE-1, and subsequent β-cleavage of APP. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 340-347, 2018.

Keywords: APP; BACE-1; amyloid beta; amyloid precursor protein; endocytosis; fluorescence complementation; protein-protein interaction; trafficking; β-site secretase protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Humans
  • Protein Transport / physiology


  • Amyloid beta-Protein Precursor
  • Amyloid Precursor Protein Secretases